Gene Symbol: Zfpm2
Description: zinc finger protein, multitype 2
Alias: B330005D23Rik, FOG-2, FOG2, zinc finger protein ZFPM2, Friend of GATA 2, friend of GATA protein 2, friend of GATA-1 2, friend of GATA-2, mFOG-2
Species: mouse
Products:     Zfpm2

Top Publications

  1. Tevosian S, Albrecht K, Crispino J, Fujiwara Y, Eicher E, Orkin S. Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2. Development. 2002;129:4627-34 pubmed
    ..We demonstrate that the transcription factor GATA4 and its co-factor FOG2 are required for gonadal differentiation...
  2. Lu J, McKinsey T, Xu H, Wang D, Richardson J, Olson E. FOG-2, a heart- and brain-enriched cofactor for GATA transcription factors. Mol Cell Biol. 1999;19:4495-502 pubmed
    ..The properties of FOG-2 suggest its involvement in the control of cardiac and neural gene expression by GATA transcription factors. ..
  3. Tevosian S, Deconinck A, Tanaka M, Schinke M, Litovsky S, Izumo S, et al. FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium. Cell. 2000;101:729-39 pubmed
    ..Our findings provide the molecular inroad into the induction of coronary vasculature by myocardium in the developing heart. ..
  4. Fox A, Liew C, Holmes M, Kowalski K, Mackay J, Crossley M. Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers. EMBO J. 1999;18:2812-22 pubmed
    ..Finally, we show that FOG-1 can repress GATA-1-mediated activation and present evidence that this ability involves the recently described CtBP co-repressor proteins that recognize all known FOG proteins. ..
  5. Svensson E, Huggins G, Dardik F, Polk C, Leiden J. A functionally conserved N-terminal domain of the friend of GATA-2 (FOG-2) protein represses GATA4-dependent transcription. J Biol Chem. 2000;275:20762-9 pubmed
  6. Svensson E, Huggins G, Lin H, Clendenin C, Jiang F, Tufts R, et al. A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2. Nat Genet. 2000;25:353-6 pubmed
    ..5 (refs 6,7). Zfpm2 (also known as Fog-2) is a multi-zinc-finger protein that is co-expressed with Gata4 in the developing heart ..
  7. Tevosian S, Deconinck A, Cantor A, Rieff H, Fujiwara Y, Corfas G, et al. FOG-2: A novel GATA-family cofactor related to multitype zinc-finger proteins Friend of GATA-1 and U-shaped. Proc Natl Acad Sci U S A. 1999;96:950-5 pubmed
    ..The interaction of GATA and FOG family members constitutes an evolutionarily conserved paradigm for transcriptional control in differentiation and organogenesis. ..
  8. Huggins G, Bacani C, Boltax J, Aikawa R, Leiden J. Friend of GATA 2 physically interacts with chicken ovalbumin upstream promoter-TF2 (COUP-TF2) and COUP-TF3 and represses COUP-TF2-dependent activation of the atrial natriuretic factor promoter. J Biol Chem. 2001;276:28029-36 pubmed
    ..Taken together, these findings suggest that FOG-2 functions as a corepressor for both GATA and COUP-TF proteins. ..
  9. Svensson E, Tufts R, Polk C, Leiden J. Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes. Proc Natl Acad Sci U S A. 1999;96:956-61 pubmed

More Information


  1. Lin A, Roche A, Wilk J, Svensson E. The N termini of Friend of GATA (FOG) proteins define a novel transcriptional repression motif and a superfamily of transcriptional repressors. J Biol Chem. 2004;279:55017-23 pubmed
    ..Taken together, these observations define a novel transcriptional repression motif and a superfamily of zinc finger transcriptional repressors. ..
  2. Crispino J, Lodish M, Thurberg B, Litovsky S, Collins T, Molkentin J, et al. Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors. Genes Dev. 2001;15:839-44 pubmed
    ..Gata4(ki/ki) mice die just after embryonic day (E) 12.5 exhibiting features in common with Fog2(-/-) embryos as well as additional semilunar cardiac valve defects and a double-outlet right ventricle...
  3. Kwan K, Lam M, Krsnik Z, Kawasawa Y, Lefebvre V, Sestan N. SOX5 postmitotically regulates migration, postmigratory differentiation, and projections of subplate and deep-layer neocortical neurons. Proc Natl Acad Sci U S A. 2008;105:16021-6 pubmed publisher
    ..Thus, SOX5 postmitotically regulates the migration, postmigratory differentiation, and subcortical projections of subplate and deep-layer neurons. ..
  4. Manuylov N, Fujiwara Y, Adameyko I, Poulat F, Tevosian S. The regulation of Sox9 gene expression by the GATA4/FOG2 transcriptional complex in dominant XX sex reversal mouse models. Dev Biol. 2007;307:356-67 pubmed
    We have previously established an in vivo requirement for GATA4 and FOG2 transcription factors in sexual differentiation...
  5. Manuylov N, Smagulova F, Tevosian S. Fog2 excision in mice leads to premature mammary gland involution and reduced Esr1 gene expression. Oncogene. 2007;26:5204-13 pubmed
    ..Here we report that in the murine mammary gland Fog2 gene expression is upregulated upon pregnancy and lactation with prominent expression in the epithelial cells of ..
  6. Smagulova F, Manuylov N, Leach L, Tevosian S. GATA4/FOG2 transcriptional complex regulates Lhx9 gene expression in murine heart development. BMC Dev Biol. 2008;8:67 pubmed publisher
    GATA4 and FOG2 proteins are required for normal cardiac development in mice...
  7. Nielsen J, Thomassen M, Møllgård K, Noraberg J, Jensen N. Zbtb20 defines a hippocampal neuronal identity through direct repression of genes that control projection neuron development in the isocortex. Cereb Cortex. 2014;24:1216-29 pubmed publisher
    ..in the developing isocortex, including Cux1, Cux2, Fezf2, Foxp2, Mef2c, Rorb, Satb2, Sox5, Tbr1, Tle4, and Zfpm2. We show that Zbtb20 represses these genes during ectopic CA1 pyramidal neuron development in transgenic mice...
  8. Fujimoto Y, Tanaka S, Yamaguchi Y, Kobayashi H, Kuroki S, Tachibana M, et al. Homeoproteins Six1 and Six4 regulate male sex determination and mouse gonadal development. Dev Cell. 2013;26:416-30 pubmed publisher
    ..Furthermore, we identified two downstream targets of Six1/Six4 in gonadal development, Fog2 (Zfpm2) and Nr5a1 (Ad4BP/Sf1)...
  9. Wiegreffe C, Simon R, Peschkes K, Kling C, Strehle M, Cheng J, et al. Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c. Neuron. 2015;87:311-25 pubmed publisher
    ..Our data uncover a novel Bcl11a/Sema3c-dependent regulatory pathway used by migrating cortical neurons. ..
  10. Gao Z, Kim G, MacKinnon A, Flagg A, Bassett B, Earley J, et al. Ets1 is required for proper migration and differentiation of the cardiac neural crest. Development. 2010;137:1543-51 pubmed publisher
  11. Manuylov N, Zhou B, Ma Q, Fox S, Pu W, Tevosian S. Conditional ablation of Gata4 and Fog2 genes in mice reveals their distinct roles in mammalian sexual differentiation. Dev Biol. 2011;353:229-41 pubmed publisher
    Assembly of functioning testis and ovary requires a GATA4-FOG2 transcriptional complex...
  12. Garnatz A, Gao Z, Broman M, Martens S, Earley J, Svensson E. FOG-2 mediated recruitment of the NuRD complex regulates cardiomyocyte proliferation during heart development. Dev Biol. 2014;395:50-61 pubmed publisher
    ..Taken together, our results define a novel mechanism in which FOG-2/NuRD interaction is required for cardiomyocyte proliferation by directly down-regulating the cell cycle inhibitor Cdkn1a during heart development. ..
  13. Laitinen M, Anttonen M, Ketola I, Wilson D, Ritvos O, Butzow R, et al. Transcription factors GATA-4 and GATA-6 and a GATA family cofactor, FOG-2, are expressed in human ovary and sex cord-derived ovarian tumors. J Clin Endocrinol Metab. 2000;85:3476-83 pubmed
    ..Our findings support a role for GATA-binding proteins in human ovarian folliculogenesis. Moreover, these data suggest that GATA factors may contribute to the phenotypes of sex cord-derived ovarian tumors...
  14. Efimenko E, Padua M, Manuylov N, Fox S, Morse D, Tevosian S. The transcription factor GATA4 is required for follicular development and normal ovarian function. Dev Biol. 2013;381:144-58 pubmed publisher
    Sex determination in mammals requires interaction between the transcription factor GATA4 and its cofactor FOG2. We have recently described the function of both proteins in testis development beyond the sex determination stage; their roles ..
  15. Flagg A, Earley J, Svensson E. FOG-2 attenuates endothelial-to-mesenchymal transformation in the endocardial cushions of the developing heart. Dev Biol. 2007;304:308-16 pubmed
    ..Taken together with GATA4's known role in promoting EMT, these results suggest that FOG-2 functions in cardiac valve formation as an attenuator of EMT by repressing GATA4 activity within the developing endocardial cushions. ..
  16. Chassot A, Bradford S, Auguste A, Gregoire E, Pailhoux E, de Rooij D, et al. WNT4 and RSPO1 together are required for cell proliferation in the early mouse gonad. Development. 2012;139:4461-72 pubmed publisher
    ..Hence, this study identifies Rspo1 and Wnt4 as two new regulators of cell proliferation in the early gonad regardless of its sex, in addition to the specific role of these genes in ovarian differentiation. ..
  17. Rouf R, Greytak S, Wooten E, Wu J, Boltax J, Picard M, et al. Increased FOG-2 in failing myocardium disrupts thyroid hormone-dependent SERCA2 gene transcription. Circ Res. 2008;103:493-501 pubmed publisher
    ..These results demonstrate that SERCA2 is an important target of FOG-2 and that increased FOG-2 expression may contribute to a decline in cardiac function in end-stage heart failure by impaired T3 signaling. ..
  18. Naillat F, Prunskaite Hyyryläinen R, Pietilä I, Sormunen R, Jokela T, Shan J, et al. Wnt4/5a signalling coordinates cell adhesion and entry into meiosis during presumptive ovarian follicle development. Hum Mol Genet. 2010;19:1539-50 pubmed publisher
    ..These findings indicate a critical role for Wnt signalling in meiosis. Thus, the Wnt signals are important somatic cell signals that coordinate presumptive female follicle development. ..
  19. Morsli H, Tuorto F, Choo D, Postiglione M, Simeone A, Wu D. Otx1 and Otx2 activities are required for the normal development of the mouse inner ear. Development. 1999;126:2335-43 pubmed
    ..These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs...
  20. Deck M, Lokmane L, Chauvet S, Mailhes C, Keita M, Niquille M, et al. Pathfinding of corticothalamic axons relies on a rendezvous with thalamic projections. Neuron. 2013;77:472-84 pubmed publisher
    ..Our study reveals that temporal control of axonal progression contributes to spatial pathfinding of cortical projections and opens perspectives on brain wiring. ..
  21. Park J, Kato M, Yuan H, Castro N, Lanting L, Wang M, et al. FOG2 protein down-regulation by transforming growth factor-?1-induced microRNA-200b/c leads to Akt kinase activation and glomerular mesangial hypertrophy related to diabetic nephropathy. J Biol Chem. 2013;288:22469-80 pubmed publisher
    ..However, the mechanisms of Akt activation by TGF-? are not fully understood. Recently, miR-200 and its target FOG2 were reported to regulate the activity of phosphatidylinositol 3-kinase (the upstream activator of Akt) in insulin ..
  22. Jacobsen C, Mannisto S, Porter Tinge S, Genova E, Parviainen H, Heikinheimo M, et al. GATA-4:FOG interactions regulate gastric epithelial development in the mouse. Dev Dyn. 2005;234:355-62 pubmed
    ..We conclude that functional interaction between GATA-4 and a member of the FOG family, presumably FOG-1, is required for proper epithelial-mesenchymal signaling in the developing stomach. ..
  23. Russell M, Longoni M, Wells J, Maalouf F, Tracy A, Loscertales M, et al. Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes. Proc Natl Acad Sci U S A. 2012;109:2978-83 pubmed publisher
  24. Mihalas A, Elsen G, Bedogni F, Daza R, Ramos Laguna K, Arnold S, et al. Intermediate Progenitor Cohorts Differentially Generate Cortical Layers and Require Tbr2 for Timely Acquisition of Neuronal Subtype Identity. Cell Rep. 2016;16:92-105 pubmed publisher
    ..Our findings indicate that upper-layer genesis depends on IPs from many stages of corticogenesis and that Tbr2 regulates the tempo of laminar fate implementation for all cortical layers. ..
  25. Zakariyah A, Rajgara R, Veinot J, Skerjanc I, Burgon P. Congenital heart defect causing mutation in Nkx2.5 displays in vivo functional deficit. J Mol Cell Cardiol. 2017;105:89-98 pubmed publisher
    ..Collectively, the present study demonstrates that mice with the R141C point mutation in the Nkx2.5 allele phenocopies humans with the NKX2.5 R142C point mutation. ..
  26. Ackerman K, Wang J, Luo L, Fujiwara Y, Orkin S, Beier D. Gata4 is necessary for normal pulmonary lobar development. Am J Respir Cell Mol Biol. 2007;36:391-7 pubmed
    Mutations of Fog2 in mice result in a phenotype that includes pulmonary lobar defects...
  27. Jack B, Crossley M. GATA proteins work together with friend of GATA (FOG) and C-terminal binding protein (CTBP) co-regulators to control adipogenesis. J Biol Chem. 2010;285:32405-14 pubmed publisher
    ..We have investigated whether FOGs and CTBPs influence adipogenesis. We found that both FOG1 and FOG2 are expressed in cells prior to adipogenesis but are down-regulated as adipogenesis proceeds...
  28. Bardot E, Calderon D, Santoriello F, Han S, Cheung K, Jadhav B, et al. Foxa2 identifies a cardiac progenitor population with ventricular differentiation potential. Nat Commun. 2017;8:14428 pubmed publisher
    ..Together, these findings provide insight into the developmental origin of ventricular and atrial cells, and may lead to the establishment of new strategies for generating chamber-specific cell types from pluripotent stem cells. ..
  29. Nemer G, Nemer M. Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6. Dev Biol. 2003;254:131-48 pubmed
    ..They also raise the possibility that part of the early defects in GATA-4 and/or GATA-6 null embryos may be due to impaired BMP-4 signaling. ..
  30. Dale R, Remo B, Svensson E. An alternative transcript of the FOG-2 gene encodes a FOG-2 isoform lacking the FOG repression motif. Biochem Biophys Res Commun. 2007;357:683-7 pubmed
    ..Together, these results suggest that FOG-2 repressive activity may be modulated by the generation of isoforms of FOG-2 lacking the FOG repression motif. ..
  31. Xiang R, Lei H, Chen M, Li Q, Sun H, Ai J, et al. The miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation of mouse embryonic cardiomyocytes. Braz J Med Biol Res. 2012;45:131-8 pubmed
    ..These results indicate that the miR-17-92 cluster regulates the expression of FOG-2 protein and suggest that the miR-17-92 cluster might play an important role in heart development. ..
  32. Leone D, Heavner W, Ferenczi E, Dobreva G, Huguenard J, Grosschedl R, et al. Satb2 Regulates the Differentiation of Both Callosal and Subcerebral Projection Neurons in the Developing Cerebral Cortex. Cereb Cortex. 2015;25:3406-19 pubmed publisher
    ..Collectively these data show that Satb2 is required by both CPNs and SCPNs for proper differentiation and axon pathfinding. ..
  33. Ackerman K, Herron B, Vargas S, Huang H, Tevosian S, Kochilas L, et al. Fog2 is required for normal diaphragm and lung development in mice and humans. PLoS Genet. 2005;1:58-65 pubmed
    ..Fog2 (Zfpm2) maps within the recombinant interval carrying the N-ethyl-N-nitrosourea-induced mutation, and DNA sequencing of ..
  34. Rawnsley D, Xiao J, Lee J, Liu X, Mericko Ishizuka P, Kumar V, et al. The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development. J Biol Chem. 2013;288:24429-40 pubmed publisher
    ..Biochemical studies reveal that ATOH8, GATA4, and FOG2 associate in a single complex in vitro...
  35. Rash B, Lim H, Breunig J, Vaccarino F. FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis. J Neurosci. 2011;31:15604-17 pubmed publisher
  36. Li Q, Wang H, Chepelev I, Zhu Q, Wei G, Zhao K, et al. Stage-dependent and locus-specific role of histone demethylase Jumonji D3 (JMJD3) in the embryonic stages of lung development. PLoS Genet. 2014;10:e1004524 pubmed publisher
    ..Our study provides molecular insights into the mechanisms by which Jmjd3 regulates target gene expression in the embryonic stages of lung development. ..
  37. Fischer A, Steidl C, Wagner T, Lang E, Jakob P, Friedl P, et al. Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition. Circ Res. 2007;100:856-63 pubmed
    ..Thus, the Hey gene family shows overlap in controlling Notch induced endocardial epithelial to mesenchymal transition, a process critical for valve and septum formation. ..
  38. Mandai K, Reimert D, Ginty D. Linx mediates interaxonal interactions and formation of the internal capsule. Neuron. 2014;83:93-103 pubmed publisher
    ..Thus, Linx guides the extension of thalamocortical axons in the ventral forebrain, and subsequently, it mediates reciprocal interactions between thalamocortical and corticofugal axons to form the IC. ..
  39. Ketola I, Anttonen M, Vaskivuo T, Tapanainen J, Toppari J, Heikinheimo M. Developmental expression and spermatogenic stage specificity of transcription factors GATA-1 and GATA-4 and their cofactors FOG-1 and FOG-2 in the mouse testis. Eur J Endocrinol. 2002;147:397-406 pubmed
    ..The findings suggest that, in contrast to the hematopoietic system and the heart, GATA-1 and GATA-4 do not use FOG-1 and FOG-2 respectively as their only cofactors during the early stages of testicular development. ..
  40. Pazin D, Albrecht K. Developmental expression of Smoc1 and Smoc2 suggests potential roles in fetal gonad and reproductive tract differentiation. Dev Dyn. 2009;238:2877-90 pubmed publisher
    ..center-to-poles wave in pre-Sertoli and pre-granulosa cells and its expression was greatly reduced in Wt1, Sf1, and Fog2 mutants. After E13...
  41. You L, Takamoto N, Yu C, Tanaka T, Kodama T, DeMayo F, et al. Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc Natl Acad Sci U S A. 2005;102:16351-6 pubmed
    ..Our finding suggests that COUP-TFII is a likely contributor to the formation of CDH in individuals with 15q deletions, and it may also be a potential contributor to some other Bochdalek-type of CDH. ..
  42. van Loenhout R, Tibboel D, Post M, Keijzer R. Congenital diaphragmatic hernia: comparison of animal models and relevance to the human situation. Neonatology. 2009;96:137-49 pubmed publisher
    ..Several animal models have been proposed to study CDH. In this review we compare surgical, pharmacological and transgenic models, and discuss their strengths and limitations to study PH. ..
  43. Shim S, Kwan K, Li M, Lefebvre V, Sestan N. Cis-regulatory control of corticospinal system development and evolution. Nature. 2012;486:74-9 pubmed publisher
    ..These findings reveal that SOX transcription factors converge onto a cis-acting element of Fezf2 and form critical components of a regulatory network controlling the identity and connectivity of corticospinal neurons. ..
  44. Katz S, Williams A, Yang J, Fujiwara Y, Tsang A, Epstein J, et al. Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development. Proc Natl Acad Sci U S A. 2003;100:14030-5 pubmed
  45. Anttonen M, Ketola I, Parviainen H, Pusa A, Heikinheimo M. FOG-2 and GATA-4 Are coexpressed in the mouse ovary and can modulate mullerian-inhibiting substance expression. Biol Reprod. 2003;68:1333-40 pubmed
    ..In postnatal ovary, granulosa cells of growing follicles express FOG-2, partially overlapping with the expression of MIS. These data suggest an important role for FOG-2 and the GATA transcription factors in the developing ovary. ..
  46. Guo Y, Yu J, Deng J, Liu B, Xiao Y, Li K, et al. A Novel Function of Hepatic FOG2 in Insulin Sensitivity and Lipid Metabolism Through PPAR?. Diabetes. 2016;65:2151-63 pubmed publisher
    b>Friend of GATA 2 (FOG2) is a transcriptional cofactor involved mostly in cardiac function. The aim of this study was to investigate the role of hepatic FOG2 in insulin sensitivity and lipid accumulation...
  47. Ross S, McCord A, Jung C, Atan D, Mok S, Hemberg M, et al. Bhlhb5 and Prdm8 form a repressor complex involved in neuronal circuit assembly. Neuron. 2012;73:292-303 pubmed publisher
    ..These findings suggest that Prdm8 is an obligate partner of Bhlhb5, forming a repressor complex that directs neural circuit assembly in part through the precise regulation of Cadherin-11. ..
  48. Bouma G, Washburn L, Albrecht K, Eicher E. Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice. Proc Natl Acad Sci U S A. 2007;104:14994-9 pubmed
    ..We report that the Fog2 and Gata4 transcription factors are haploinsufficient for testis determination in mice...
  49. Huang J, Peng J, Cao G, Lu S, Liu L, Li Z, et al. Hypoxia-Induced MicroRNA-429 Promotes Differentiation of MC3T3-E1 Osteoblastic Cells by Mediating ZFPM2 Expression. Cell Physiol Biochem. 2016;39:1177-86 pubmed publisher
    ..To test whether miR-429 directly regulate the expression level of ZFPM2 at transcription level, dual-luciferase reporter gene assay was performed...
  50. Kask K, Ruisu K, Tikker L, Karis K, Saare M, Meier R, et al. Deletion of RIC8A in neural precursor cells leads to altered neurogenesis and neonatal lethality of mouse. Dev Neurobiol. 2015;75:984-1002 pubmed publisher
    ..Taken together, RIC8A has an essential role in the development of mammalian nervous system by maintaining the integrity of pial basement membrane and modulating cell division. ..
  51. Mei S, Xin J, Liu Y, Zhang Y, Liang X, Su X, et al. MicroRNA-200c Promotes Suppressive Potential of Myeloid-Derived Suppressor Cells by Modulating PTEN and FOG2 Expression. PLoS ONE. 2015;10:e0135867 pubmed publisher
    ..expansion and immune suppressive activity of MDSCs via targeting phosphatase and tensin homolog (PTEN) and friend of Gata 2 (FOG2), which can lead to STAT3 and PI3K/Akt activation...
  52. Watanabe T, Koibuchi N, Chin M. Transcription factor CHF1/Hey2 regulates coronary vascular maturation. Mech Dev. 2010;127:418-27 pubmed publisher
    ..These findings suggest that CHF1/Hey2 regulates the later steps of coronary vascular development in both a myocardial-dependent, non-cell autonomous fashion and likely a vascular cell-specific effect as well. ..
  53. Jay P, Bielinska M, Erlich J, Mannisto S, Pu W, Heikinheimo M, et al. Impaired mesenchymal cell function in Gata4 mutant mice leads to diaphragmatic hernias and primary lung defects. Dev Biol. 2007;301:602-14 pubmed
    ..Analysis of wild-type mouse embryos demonstrated co-expression of Gata4 and Fog2 in mesenchymal cells of the developing diaphragm, lungs, and heart...