Aldh1a2

Summary

Gene Symbol: Aldh1a2
Description: aldehyde dehydrogenase family 1, subfamily A2
Alias: AV116159, Aldh1a7, Raldh1, Raldh2, retinal dehydrogenase 2, RALDH 2, RALDH(II), alcohol dehydrogenase family 1, subfamily A2, alcohol dehydrogenase family 1, subfamily A7, aldehyde dehydrogenase family 1 member A2, retinaldehyde dehydrogenase 2, retinaldehyde-specific dehydrogenase type 2
Species: mouse
Products:     Aldh1a2

Top Publications

  1. Niederreither K, Vermot J, Schuhbaur B, Chambon P, Dolle P. Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse. Development. 2002;129:3563-74 pubmed
    ..lack of endogenous RA synthesis affects limb morphogenesis in mutant mouse embryos deficient for the retinaldehyde dehydrogenase 2 (Raldh2/Aldh1a2)...
  2. LaMantia A, Bhasin N, Rhodes K, Heemskerk J. Mesenchymal/epithelial induction mediates olfactory pathway formation. Neuron. 2000;28:411-25 pubmed
    ..Thus, a cellular and molecular mechanism that facilitates musculoskeletal and vascular development elsewhere in the embryo has been adapted to guide the differentiation of the olfactory pathway in the developing forebrain. ..
  3. Tschopp P, Christen A, Duboule D. Bimodal control of Hoxd gene transcription in the spinal cord defines two regulatory subclusters. Development. 2012;139:929-39 pubmed publisher
  4. Niederreither K, Vermot J, Messaddeq N, Schuhbaur B, Chambon P, Dolle P. Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse. Development. 2001;128:1019-31 pubmed
    ..To block endogenous RA synthesis, we have disrupted the gene encoding RALDH2, the first retinaldehyde dehydrogenase whose expression has been detected during early mouse post-implantation ..
  5. Mic F, Molotkov A, Molotkova N, Duester G. Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation. Dev Dyn. 2004;231:270-7 pubmed
    Three retinaldehyde dehydrogenase genes (Raldh1, Raldh2, and Raldh3) expressed in unique spatiotemporal patterns may control synthesis of retinoic acid (RA) needed for retina development...
  6. Vermot J, Gallego Llamas J, Fraulob V, Niederreither K, Chambon P, Dolle P. Retinoic acid controls the bilateral symmetry of somite formation in the mouse embryo. Science. 2005;308:563-6 pubmed
    ..These data implicate retinoic acid as an endogenous signal that maintains the bilateral synchrony of mesoderm segmentation, and therefore controls bilateral symmetry, in vertebrate embryos. ..
  7. Zhao X, Duester G. Effect of retinoic acid signaling on Wnt/beta-catenin and FGF signaling during body axis extension. Gene Expr Patterns. 2009;9:430-5 pubmed publisher
    ..occurs in between in the trunk under the control of the RA-synthesizing enzyme retinaldehyde dehydrogenase-2 (Raldh2)...
  8. Touma S, Perner S, Rubin M, Nanus D, Gudas L. Retinoid metabolism and ALDH1A2 (RALDH2) expression are altered in the transgenic adenocarcinoma mouse prostate model. Biochem Pharmacol. 2009;78:1127-38 pubmed publisher
    ..RT-PCR to measure transcripts for genes involved in retinoid signaling and metabolism, including ALDH1A1, ALDH1A2, ALDH1A3, CYP26A1, LRAT, and RARbeta(2), in prostate tissue from TRAMP positive (+) and age-matched littermate ..
  9. Li H, Wagner E, McCaffery P, Smith D, Andreadis A, Drager U. A retinoic acid synthesizing enzyme in ventral retina and telencephalon of the embryonic mouse. Mech Dev. 2000;95:283-9 pubmed
    Most retinoic acid (RA) in the embryonic mouse is generated by three retinaldehyde dehydrogenases (RALDHs). RALDH1 (also called E1, AHD2 or ALDH1) is expressed in the dorsal retina, and RALDH2 (V2, ALDH11) generates most RA in the ..

More Information

Publications63

  1. Cunningham T, Zhao X, Duester G. Uncoupling of retinoic acid signaling from tailbud development before termination of body axis extension. Genesis. 2011;49:776-83 pubmed publisher
    During the early stages of body axis extension, retinoic acid (RA) synthesized in somites by Raldh2 represses caudal fibroblast growth factor (FGF) signaling to limit the tailbud progenitor zone...
  2. Niederreither K, Vermot J, Schuhbaur B, Chambon P, Dolle P. Retinoic acid synthesis and hindbrain patterning in the mouse embryo. Development. 2000;127:75-85 pubmed
    Targeted disruption of the murine retinaldehyde dehydrogenase 2 (Raldh2) gene precludes embryonic retinoic acid (RA) synthesis, leading to midgestational lethality (Niederreither, K., Subbarayan, V., Dolle, P. and Chambon, P. (1999)...
  3. Paschaki M, Lin S, Wong R, Finnell R, Dolle P, Niederreither K. Retinoic acid-dependent signaling pathways and lineage events in the developing mouse spinal cord. PLoS ONE. 2012;7:e32447 pubmed publisher
    ..Here we use Raldh2-null mouse mutants rescued from early embryonic lethality to study the consequences of lack of endogenous retinoic ..
  4. Niederreither K, Subbarayan V, Dolle P, Chambon P. Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nat Genet. 1999;21:444-8 pubmed
    ..Here we show that production of RA by the retinaldehyde dehydrogenase-2 (Raldh2) enzyme is required for mouse embryo survival and early morphogenesis...
  5. Levinson R, Batourina E, Choi C, Vorontchikhina M, Kitajewski J, Mendelsohn C. Foxd1-dependent signals control cellularity in the renal capsule, a structure required for normal renal development. Development. 2005;132:529-39 pubmed
  6. Niederreither K, McCaffery P, Drager U, Chambon P, Dolle P. Restricted expression and retinoic acid-induced downregulation of the retinaldehyde dehydrogenase type 2 (RALDH-2) gene during mouse development. Mech Dev. 1997;62:67-78 pubmed
    ..Administration of a teratogenic dose of RA at embryonic day 8.5 results in downregulation of RALDH-2 transcript levels in caudal regions of the embryo, and may reflect a mechanism of negative feedback regulation of RA synthesis. ..
  7. Wagner E, McCaffery P, Drager U. Retinoic acid in the formation of the dorsoventral retina and its central projections. Dev Biol. 2000;222:460-70 pubmed
    ..These observations indicate that the dorsoventral axis of the embryonic eye anlage determines the functional coordinates of both vision and eye movements in the adult. ..
  8. Chatzi C, Brade T, Duester G. Retinoic acid functions as a key GABAergic differentiation signal in the basal ganglia. PLoS Biol. 2011;9:e1000609 pubmed publisher
    ..in the subventricular zone of the basal ganglia is required for GABAergic differentiation, whereas RA generated by Raldh2 in the meninges is unnecessary for development of the adjacent cortex...
  9. Raverdeau M, Gely Pernot A, Féret B, Dennefeld C, Benoit G, Davidson I, et al. Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis. Proc Natl Acad Sci U S A. 2012;109:16582-7 pubmed publisher
  10. Tarchini B, Huynh T, Cox G, Duboule D. HoxD cluster scanning deletions identify multiple defects leading to paralysis in the mouse mutant Ironside. Genes Dev. 2005;19:2862-76 pubmed
    ..These results highlight the importance of a systematic approach when studying such clustered gene families, and give insights into the function and regulation of Hox and Evx2 genes during early spinal cord development. ..
  11. Zhao X, Brade T, Cunningham T, Duester G. Retinoic acid controls expression of tissue remodeling genes Hmgn1 and Fgf18 at the digit-interdigit junction. Dev Dyn. 2010;239:665-71 pubmed publisher
    ..Here, we report that the RA-generating enzyme retinaldehyde dehydrogenase-2 (Raldh2) is expressed in the interdigital mesenchyme whereas Cyp26b1, controlling RA degradation, is expressed in digits, ..
  12. Uehara M, Yashiro K, Takaoka K, Yamamoto M, Hamada H. Removal of maternal retinoic acid by embryonic CYP26 is required for correct Nodal expression during early embryonic patterning. Genes Dev. 2009;23:1689-98 pubmed publisher
    ..These observations suggest that maternal RA must be removed by embryonic CYP26 for correct Nodal expression during embryonic patterning. ..
  13. Mesbah K, Harrelson Z, Théveniau Ruissy M, Papaioannou V, Kelly R. Tbx3 is required for outflow tract development. Circ Res. 2008;103:743-50 pubmed publisher
  14. Ji S, Zhuang B, Falco C, Schneider A, Schuster Gossler K, Gossler A, et al. Mesodermal and neuronal retinoids regulate the induction and maintenance of limb innervating spinal motor neurons. Dev Biol. 2006;297:249-61 pubmed
    ..These findings suggest that during embryogenesis, mesodermal and neuronal retinoids act coordinately to establish and maintain appropriate cohorts of spinal motor neurons that innervate target muscles in the limb. ..
  15. Desai T, Malpel S, Flentke G, Smith S, Cardoso W. Retinoic acid selectively regulates Fgf10 expression and maintains cell identity in the prospective lung field of the developing foregut. Dev Biol. 2004;273:402-15 pubmed
    ..Our study supports RA as an essential regulator of gene expression and cellular activities during primary bud formation. ..
  16. Yashiro K, Zhao X, Uehara M, Yamashita K, Nishijima M, Nishino J, et al. Regulation of retinoic acid distribution is required for proximodistal patterning and outgrowth of the developing mouse limb. Dev Cell. 2004;6:411-22 pubmed
    ..These observations suggest that RA acts as a morphogen to determine proximodistal identity, and that CYP26B1 prevents apoptosis and promotes chondrocyte maturation, in the developing limb. ..
  17. Matt N, Dupé V, Garnier J, Dennefeld C, Chambon P, Mark M, et al. Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells. Development. 2005;132:4789-800 pubmed
    ..is not the retina nor the corneal ectoderm, which both express RA-synthesizing retinaldehyde dehydrogenases (RALDH1 and RALDH3), but the neural crest cell-derived periocular mesenchyme (POM), which is devoid of RALDH...
  18. Serpente P, Tümpel S, Ghyselinck N, Niederreither K, Wiedemann L, Dolle P, et al. Direct crossregulation between retinoic acid receptor {beta} and Hox genes during hindbrain segmentation. Development. 2005;132:503-13 pubmed
    ..We propose that the function of this circuit is to align the initially incongruent expression of multiple RA-induced genes at a single segment boundary. ..
  19. Sirbu I, Zhao X, Duester G. Retinoic acid controls heart anteroposterior patterning by down-regulating Isl1 through the Fgf8 pathway. Dev Dyn. 2008;237:1627-35 pubmed publisher
    ..Here, we demonstrate that Raldh2(-/-) mouse embryos lacking retinoic acid signaling exhibit a posterior expansion of the cardiac Fgf8 expression ..
  20. Molotkova N, Molotkov A, Duester G. Role of retinoic acid during forebrain development begins late when Raldh3 generates retinoic acid in the ventral subventricular zone. Dev Biol. 2007;303:601-10 pubmed
    ..Similar expression of Raldh3 exists in E8.75 mouse embryos, but Raldh2 is also expressed in the optic vesicle at this stage suggesting that both genes may play a role in early forebrain ..
  21. Molotkov A, Molotkova N, Duester G. Retinoic acid guides eye morphogenetic movements via paracrine signaling but is unnecessary for retinal dorsoventral patterning. Development. 2006;133:1901-10 pubmed
    ..Here, we report Raldh1, Raldh2 and Raldh3 single, double and triple null mice exhibiting progressively less or no RA synthesis in the eye...
  22. Mic F, Haselbeck R, Cuenca A, Duester G. Novel retinoic acid generating activities in the neural tube and heart identified by conditional rescue of Raldh2 null mutant mice. Development. 2002;129:2271-82 pubmed
    ..The RA biosynthetic enzyme RALDH2 catalyzes much, but not all, RA production in mouse embryos, as revealed here with Raldh2 null mutants carrying an ..
  23. Castillo H, Cravo R, Azambuja A, Simões Costa M, Sura Trueba S, Gonzalez J, et al. Insights into the organization of dorsal spinal cord pathways from an evolutionarily conserved raldh2 intronic enhancer. Development. 2010;137:507-18 pubmed publisher
    Comparative studies of the tetrapod raldh2 (aldh1a2) gene, which encodes a retinoic acid (RA) synthesis enzyme, have led to the identification of a dorsal spinal cord enhancer...
  24. Martin M, Gallego Llamas J, Ribes V, Kedinger M, Niederreither K, Chambon P, et al. Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant mice. Dev Biol. 2005;284:399-411 pubmed
    ..mouse pancreas development, we have studied the phenotype of mice with a targeted deletion in the retinaldehyde dehydrogenase 2 (Raldh2) gene, encoding the enzyme required to synthesize RA in the embryo...
  25. Vermot J, Pourquie O. Retinoic acid coordinates somitogenesis and left-right patterning in vertebrate embryos. Nature. 2005;435:215-20 pubmed
    ..Our data indicate that RA is important in buffering the lateralizing influence of the left-right machinery, thus permitting synchronization of the development of the two embryonic sides. ..
  26. Wang X, Sperkova Z, Napoli J. Analysis of mouse retinal dehydrogenase type 2 promoter and expression. Genomics. 2001;74:245-50 pubmed
    The mouse RALDH2 gene spans >50 kb, has a structure similar to that of human class 1 aldehyde dehydrogenase genes, and localizes to the central region of chromosome 9 by single-strand polymorphism analysis...
  27. Zhao X, Sirbu I, Mic F, Molotkova N, Molotkov A, Kumar S, et al. Retinoic acid promotes limb induction through effects on body axis extension but is unnecessary for limb patterning. Curr Biol. 2009;19:1050-7 pubmed publisher
    ..Here, we utilize Raldh2-/- and Raldh3-/- mouse embryos lacking RA synthesis to demonstrate that RA signaling is not required for limb ..
  28. Mic F, Molotkov A, Fan X, Cuenca A, Duester G. RALDH3, a retinaldehyde dehydrogenase that generates retinoic acid, is expressed in the ventral retina, otic vesicle and olfactory pit during mouse development. Mech Dev. 2000;97:227-30 pubmed
    ..The developmental expression patterns of two ALDHs that function as retinaldehyde dehydrogenases, RALDH1 and RALDH2, have been described...
  29. Wu Y, Wang G, Scott S, Capecchi M. Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons. Development. 2008;135:171-82 pubmed
    ..Together, these results show that Hoxc10 and Hoxd10 play key roles in establishing lumbar motoneuron columnar, divisional and motor pool identity. ..
  30. Siegenthaler J, Ashique A, Zarbalis K, Patterson K, Hecht J, KANE M, et al. Retinoic acid from the meninges regulates cortical neuron generation. Cell. 2009;139:597-609 pubmed publisher
    ..In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had ..
  31. Niederreither K, Vermot J, Fraulob V, Chambon P, Dolle P. Retinaldehyde dehydrogenase 2 (RALDH2)- independent patterns of retinoic acid synthesis in the mouse embryo. Proc Natl Acad Sci U S A. 2002;99:16111-6 pubmed
    Knockout of the murine retinoic acid (RA)-synthesizing enzyme retinaldehyde dehydrogenase 2 (RALDH2) gene leads to early morphogenetic defects and embryonic lethality...
  32. Kumar S, Duester G. Retinoic acid controls body axis extension by directly repressing Fgf8 transcription. Development. 2014;141:2972-7 pubmed publisher
    ..Epigenetic analysis using chromatin immunoprecipitation of trunk tissues from E8.25 wild-type and Raldh2(-/-) embryos lacking RA synthesis revealed RA-dependent recruitment of the repressive histone marker H3K27me3 and ..
  33. Sapin V, Ward S, Bronner S, Chambon P, Dolle P. Differential expression of transcripts encoding retinoid binding proteins and retinoic acid receptors during placentation of the mouse. Dev Dyn. 1997;208:199-210 pubmed
    ..5 dpc, whereas RXR alpha exhibits a strong expression in this zone until birth, suggesting a role for these receptors in the development and function of the definitive placenta. ..
  34. Hsu L, Chang W, Yoshida A. Mouse type-2 retinaldehyde dehydrogenase (RALDH2): genomic organization, tissue-dependent expression, chromosome assignment and comparison to other types. Biochim Biophys Acta. 2000;1492:289-93 pubmed
    ..We determined the structural organization of mouse type-2 Raldh2 by isolation of overlapping genomic DNA clones from a phage library...
  35. Vermot J, Schuhbaur B, Le Mouellic H, McCaffery P, Garnier J, Hentsch D, et al. Retinaldehyde dehydrogenase 2 and Hoxc8 are required in the murine brachial spinal cord for the specification of Lim1+ motoneurons and the correct distribution of Islet1+ motoneurons. Development. 2005;132:1611-21 pubmed
    ..and early differentiation using a conditional knockout strategy that ablates the function of the retinaldehyde dehydrogenase 2 (Raldh2) synthesizing enzyme essentially in brachial motoneurons, and later in mesenchymal cells at ..
  36. Chia I, Grote D, Marcotte M, Batourina E, Mendelsohn C, Bouchard M. Nephric duct insertion is a crucial step in urinary tract maturation that is regulated by a Gata3-Raldh2-Ret molecular network in mice. Development. 2011;138:2089-97 pubmed publisher
    ..We find a similar set of malformations in mutants lacking either Gata3 or Raldh2. We show that these factors act in parallel to regulate ND insertion via Ret...
  37. Norden J, Grieskamp T, Lausch E, van Wijk B, van den Hoff M, Englert C, et al. Wt1 and retinoic acid signaling in the subcoelomic mesenchyme control the development of the pleuropericardial membranes and the sinus horns. Circ Res. 2010;106:1212-20 pubmed publisher
    ..Expression of the Raldh2 (aldehyde dehydrogenase family 1, subfamily A2) gene was lost from this mesenchyme in Wt1(-/-) embryos...
  38. Niederreither K, Fraulob V, Garnier J, Chambon P, Dolle P. Differential expression of retinoic acid-synthesizing (RALDH) enzymes during fetal development and organ differentiation in the mouse. Mech Dev. 2002;110:165-71 pubmed
    Three retinaldehyde dehydrogenases (RALDH1, RALDH2 and RALDH3), which catalyze the oxidation of retinaldehyde into retinoic acid, have been shown to be differentially expressed during early embryogenesis...
  39. Rhinn M, Schuhbaur B, Niederreither K, Dolle P. Involvement of retinol dehydrogenase 10 in embryonic patterning and rescue of its loss of function by maternal retinaldehyde treatment. Proc Natl Acad Sci U S A. 2011;108:16687-92 pubmed publisher
    ..These results underscore the importance of maternal retinoids in preventing congenital birth defects, and lead to a revised model of the importance of RDH10 and RALDHs in controlling embryonic RA distribution...
  40. Vezina C, Allgeier S, Fritz W, Moore R, Strerath M, Bushman W, et al. Retinoic acid induces prostatic bud formation. Dev Dyn. 2008;237:1321-33 pubmed publisher
    ..These observations suggest that reciprocal changes in hedgehog and BMP signaling by RA may regulate bud initiation. ..
  41. Sirbu I, Duester G. Retinoic-acid signalling in node ectoderm and posterior neural plate directs left-right patterning of somitic mesoderm. Nat Cell Biol. 2006;8:271-7 pubmed
    ..depends on opposing signalling gradients of retinoic acid (generated by retinaldehyde dehydrogenase-2; Raldh2) anteriorly and fibroblast growth factor (FGF; generated by Fgf8) posteriorly...
  42. Niederreither K, Abu Abed S, Schuhbaur B, Petkovich M, Chambon P, Dolle P. Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development. Nat Genet. 2002;31:84-8 pubmed
    ..We show that Cyp26a1(-/-) mice are phenotypically rescued by heterozygous disruption of Aldh1a2 (also known as Raldh2), which encodes a retinaldehyde dehydrogenase responsible for the synthesis of retinoic ..
  43. Acharya A, Baek S, Huang G, Eskiocak B, Goetsch S, Sung C, et al. The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors. Development. 2012;139:2139-49 pubmed publisher
    ..We demonstrate a unique role for Tcf21 in multipotent epicardial progenitors, prior to the process of EMT that is essential for cardiac fibroblast development...
  44. Self M, Lagutin O, Bowling B, Hendrix J, Cai Y, Dressler G, et al. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J. 2006;25:5214-28 pubmed
    ..We propose that in the developing kidney, Six2 activity is required for maintaining the mesenchymal progenitor population in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud...
  45. Arber S, Han B, Mendelsohn M, Smith M, Jessell T, Sockanathan S. Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron. 1999;23:659-74 pubmed
    ..These findings show that HB9 has an essential function in consolidating the identity of postmitotic MNs. ..
  46. Levi B, Yilmaz O, Duester G, Morrison S. Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems. Blood. 2009;113:1670-80 pubmed publisher
    ..Finally, Aldh1a1 deficiency did not affect the function of stem cells from the adult central or peripheral nervous systems. Aldh1a1 is not a critical regulator of adult stem cell function or Aldefluor staining in mice. ..
  47. Sandell L, Iulianella A, Melton K, Lynn M, Walker M, Inman K, et al. A phenotype-driven ENU mutagenesis screen identifies novel alleles with functional roles in early mouse craniofacial development. Genesis. 2011;49:342-59 pubmed publisher
  48. Corcoran J, Maden M. Nerve growth factor acts via retinoic acid synthesis to stimulate neurite outgrowth. Nat Neurosci. 1999;2:307-8 pubmed
  49. Molotkova N, Molotkov A, Sirbu I, Duester G. Requirement of mesodermal retinoic acid generated by Raldh2 for posterior neural transformation. Mech Dev. 2005;122:145-55 pubmed
    ..We have tested this hypothesis in retinaldehyde dehydrogenase-2 (Raldh2) null mutant mice lacking RA synthesis in the somitic mesoderm...
  50. Niederreither K, Vermot J, Le Roux I, Schuhbaur B, Chambon P, Dolle P. The regional pattern of retinoic acid synthesis by RALDH2 is essential for the development of posterior pharyngeal arches and the enteric nervous system. Development. 2003;130:2525-34 pubmed
    Targeted inactivation of the mouse retinaldehyde dehydrogenase 2 (RALDH2/ALDH1a2), the enzyme responsible for early embryonic retinoic acid synthesis, is embryonic lethal because of defects in early heart morphogenesis...
  51. Ryckebusch L, Wang Z, Bertrand N, Lin S, Chi X, Schwartz R, et al. Retinoic acid deficiency alters second heart field formation. Proc Natl Acad Sci U S A. 2008;105:2913-8 pubmed publisher
    ..The retinaldehyde dehydrogenase 2 (RALDH2) enzyme catalyzes the second oxidative step in RA biosynthesis and its loss of function ..
  52. Molotkov A, Molotkova N, Duester G. Retinoic acid generated by Raldh2 in mesoderm is required for mouse dorsal endodermal pancreas development. Dev Dyn. 2005;232:950-7 pubmed
    ..We have analyzed mouse embryos carrying a null mutation of the gene encoding retinaldehyde dehydrogenase 2 (Raldh2), which controls RA synthesis...
  53. Bangs F, Antonio N, Thongnuek P, Welten M, Davey M, Briscoe J, et al. Generation of mice with functional inactivation of talpid3, a gene first identified in chicken. Development. 2011;138:3261-72 pubmed publisher
    ..talpid(3) chicken limbs, the mutant mouse limbs are syndactylous with uneven digit spacing as reflected in altered Raldh2 expression, which is normally associated with interdigital mesenchyme...
  54. Bowles J, Knight D, Smith C, Wilhelm D, Richman J, Mamiya S, et al. Retinoid signaling determines germ cell fate in mice. Science. 2006;312:596-600 pubmed
    ..Thus, precise regulation of retinoid levels during fetal gonad development provides the molecular control mechanism that specifies germ cell fate. ..