Gene Symbol: phox2bb
Description: paired-like homeobox 2bb
Alias: phox2b, paired mesoderm homeobox protein 2B, paired-like homeobox 2b
Species: zebrafish
Products:     phox2bb

Top Publications

  1. Shepherd I, Pietsch J, Elworthy S, Kelsh R, Raible D. Roles for GFRalpha1 receptors in zebrafish enteric nervous system development. Development. 2004;131:241-9 pubmed
    ..Phenotypes induced by injection of antisense morpholinos against both Gfra orthologs can be rescued by introduction of mRNA for gfra1a or for gfra2, suggesting that GFRalpha1 and GFRalpha2 are functionally equivalent. ..
  2. Nechiporuk A, Linbo T, Raible D. Endoderm-derived Fgf3 is necessary and sufficient for inducing neurogenesis in the epibranchial placodes in zebrafish. Development. 2005;132:3717-30 pubmed
    ..Based on these findings, we propose a model for epibranchial placode development in which Fgf3 is a major endodermal determinant required for epibranchial placode neurogenesis. ..
  3. Holzschuh J, Wada N, Wada C, Schaffer A, Javidan Y, Tallafuss A, et al. Requirements for endoderm and BMP signaling in sensory neurogenesis in zebrafish. Development. 2005;132:3731-42 pubmed
    ..Our results show that the endoderm regulates the differentiation of cranial sensory ganglia, which coordinates the cranial nerves with the segments that they innervate...
  4. Stewart R, Arduini B, Berghmans S, George R, Kanki J, Henion P, et al. Zebrafish foxd3 is selectively required for neural crest specification, migration and survival. Dev Biol. 2006;292:174-88 pubmed
  5. Lucas M, Muller F, Rüdiger R, Henion P, Rohrer H. The bHLH transcription factor hand2 is essential for noradrenergic differentiation of sympathetic neurons. Development. 2006;133:4015-24 pubmed
    The basic helix-loop-helix transcription factor Hand2, together with Ascl1, Phox2a, Phox2b and Gata2/Gata3, is induced by bone morphogenetic proteins in neural crest-derived precursor cells during sympathetic neuron generation...
  6. Nechiporuk A, Linbo T, Poss K, Raible D. Specification of epibranchial placodes in zebrafish. Development. 2007;134:611-23 pubmed
    ..The coordinated interplay between craniofacial tissues would thus assure proper spatial and temporal interactions in the shaping of the vertebrate head...
  7. McGaughey D, Vinton R, Huynh J, Al Saif A, Beer M, McCallion A. Metrics of sequence constraint overlook regulatory sequences in an exhaustive analysis at phox2b. Genome Res. 2008;18:252-60 pubmed
    ..We have tiled across sequence encompassing the zebrafish phox2b gene, ultimately evaluating 48 amplicons corresponding to all noncoding sequences therein for enhancer activity in ..
  8. Tobin J, Di Franco M, Eichers E, May Simera H, Garcia M, Yan J, et al. Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet-Biedl syndrome. Proc Natl Acad Sci U S A. 2008;105:6714-9 pubmed publisher
    ..Moreover, this is a previously undescribed method of using characterization of facial dysmorphology as a basis for investigating the pathomechanism of CF development in dysmorphic syndromes...
  9. Elworthy S, Pinto J, Pettifer A, Cancela M, Kelsh R. Phox2b function in the enteric nervous system is conserved in zebrafish and is sox10-dependent. Mech Dev. 2005;122:659-69 pubmed
    ..Here, we characterize zebrafish phox2b as a functionally conserved marker of the developing ENS...

More Information


  1. Lister J, Cooper C, Nguyen K, Modrell M, Grant K, Raible D. Zebrafish Foxd3 is required for development of a subset of neural crest derivatives. Dev Biol. 2006;290:92-104 pubmed
  2. Guo S, Brush J, Teraoka H, Goddard A, Wilson S, Mullins M, et al. Development of noradrenergic neurons in the zebrafish hindbrain requires BMP, FGF8, and the homeodomain protein soulless/Phox2a. Neuron. 1999;24:555-66 pubmed
    ..Phox2a is not only necessary but also sufficient to induce Phox2b+ dopamine-beta-hydroxylase+ and tyrosine hydroxylase+ NA neurons in ectopic locations...
  3. Hans S, Irmscher A, Brand M. Zebrafish Foxi1 provides a neuronal ground state during inner ear induction preceding the Dlx3b/4b-regulated sensory lineage. Development. 2013;140:1936-45 pubmed publisher
    ..Thus, in addition to otic fate Foxi1 provides neuronal competence during OEPD induction prior to and independently of the Dlx3b/4b-mediated sensory fate of the developing inner ear. ..
  4. Zakhary S, Ayubcha D, Ansari F, Kamran K, Karim M, Leheste J, et al. A behavioral and molecular analysis of ketamine in zebrafish. Synapse. 2011;65:160-7 pubmed publisher
    ..In addition, we revealed that the transcription factor Phox2b is a molecular substrate for the actions of ketamine, particularly during periods of hypoxic stress...
  5. McGaughey D, McCallion A. Efficient discovery of ASCL1 regulatory sequences through transgene pooling. Genomics. 2010;95:363-9 pubmed publisher
    ..These data demonstrate the utility of this approach and its potential for further adaptation and higher throughput application. ..
  6. McGaughey D, Stine Z, Huynh J, Vinton R, McCallion A. Asymmetrical distribution of non-conserved regulatory sequences at PHOX2B is reflected at the ENCODE loci and illuminates a possible genome-wide trend. BMC Genomics. 2009;10:8 pubmed publisher
    ..Recent in vitro observations from the ENCODE project combined with in vivo analyses at the zebrafish phox2b locus suggests that a significant fraction of regulatory elements may fall below commonly applied metrics of ..
  7. Delalande J, Guyote M, Smith C, Shepherd I. Zebrafish sip1a and sip1b are essential for normal axial and neural patterning. Dev Dyn. 2008;237:1060-9 pubmed publisher
    ..This results in a subsequent absence of neural crest precursors in the posterior pharyngeal arches and a loss of enteric precursors in the intestine. ..
  8. Taylor C, Montagne W, Eisen J, Ganz J. Molecular fingerprinting delineates progenitor populations in the developing zebrafish enteric nervous system. Dev Dyn. 2016;245:1081-1096 pubmed publisher
    ..dependent progenitor subpopulations based on coexpression of three genes essential for normal ENS development: phox2bb, sox10, and ret...
  9. Uribe R, Bronner M. Meis3 is required for neural crest invasion of the gut during zebrafish enteric nervous system development. Mol Biol Cell. 2015;26:3728-40 pubmed publisher
    ..Taken together, these findings support a model in which Meis3 is required for neural crest proliferation, migration into, and colonization of the gut such that its loss leads to severe defects in enteric nervous system development. ..
  10. Delfino Machin M, Madelaine R, Busolin G, Nikaido M, Colanesi S, Camargo Sosa K, et al. Sox10 contributes to the balance of fate choice in dorsal root ganglion progenitors. PLoS ONE. 2017;12:e0172947 pubmed publisher
    ..Sox10 is thus a key transcription factor in achieving the balance of sensory neuronal and glial fates. ..
  11. Tao T, Sondalle S, Shi H, Zhu S, Perez Atayde A, Peng J, et al. The pre-rRNA processing factor DEF is rate limiting for the pathogenesis of MYCN-driven neuroblastoma. Oncogene. 2017;36:3852-3867 pubmed publisher
    ..Our results indicate that DEF and possibly other components of the SSU processome provide a novel site of vulnerability in neuroblastoma cells that could be exploited for targeted therapy. ..
  12. Roy Carson S, Natukunda K, Chou H, Pal N, Farris C, Schneider S, et al. Defining the transcriptomic landscape of the developing enteric nervous system and its cellular environment. BMC Genomics. 2017;18:290 pubmed publisher
    ..genes that drive specification, differentiation and the neural circuitry of specific neural progenitors, the phox2b expressing ENS cell lineage, during normal enteric nervous system development...
  13. Cheng W, Tang C, Gui H, So M, Lui V, Tam P, et al. Depletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype. World J Gastroenterol. 2015;21:2040-6 pubmed publisher
    ..We also studied the expressions of ret and phox2bb, which are involved in ENS development, in the ikbkap morpholino injected embryos by quantitative reverse ..
  14. Harrison C, Wabbersen T, Shepherd I. In vivo visualization of the development of the enteric nervous system using a Tg(-8.3bphox2b:Kaede) transgenic zebrafish. Genesis. 2014;52:985-90 pubmed publisher
    The phox2b gene encodes a transcription factor that is expressed in the developing enteric nervous system (ENS)...
  15. Doodnath R, Dervan A, Wride M, Puri P. Zebrafish: an exciting model for investigating the spatio-temporal pattern of enteric nervous system development. Pediatr Surg Int. 2010;26:1217-21 pubmed publisher
    ..Antibodies to Phox2b were used to identify enteric neurons...
  16. Zhu S, Lee J, Guo F, Shin J, Perez Atayde A, Kutok J, et al. Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell. 2012;21:362-73 pubmed publisher
    ..Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts, thus promoting progression to neuroblastoma...
  17. de Jong Curtain T, Parslow A, Trotter A, Hall N, Verkade H, Tabone T, et al. Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-deficient zebrafish. Gastroenterology. 2009;136:902-11 pubmed publisher
    ..Cells in these tissues display disrupted nuclear pore formation; ultimately, intestinal epithelial cells undergo apoptosis. Our results demonstrate that Elys regulates digestive organ formation. ..
  18. Olden T, Akhtar T, Beckman S, Wallace K. Differentiation of the zebrafish enteric nervous system and intestinal smooth muscle. Genesis. 2008;46:484-98 pubmed publisher
    ..Numbers of enteric neurons increase gradually except during periods of circular and longitudinal intestinal smooth muscle differentiation. ..
  19. Lopes S, Yang X, Müller J, Carney T, McAdow A, Rauch G, et al. Leukocyte tyrosine kinase functions in pigment cell development. PLoS Genet. 2008;4:e1000026 pubmed publisher
    ..In summary, we have discovered a novel signalling pathway in NCC development and demonstrate fate specification of iridophores as the first identified role for Ltk. ..
  20. Coppola E, D Autréaux F, Nomaksteinsky M, Brunet J. Phox2b expression in the taste centers of fish. J Comp Neurol. 2012;520:3633-49 pubmed publisher
    The homeodomain transcription factor Phox2b controls the formation of the sensory-motor reflex circuits of the viscera in vertebrates...
  21. Roach G, Heath Wallace R, Cameron A, Emrah Ozel R, Hongay C, Baral R, et al. Loss of ascl1a prevents secretory cell differentiation within the zebrafish intestinal epithelium resulting in a loss of distal intestinal motility. Dev Biol. 2013;376:171-86 pubmed publisher
    ..Loss of enteroendocrine cells reveals the critical need for enteroendocrine products in maintenance of normal intestinal motility. ..
  22. Ignatius M, Unal Eroglu A, Malireddy S, Gallagher G, Nambiar R, Henion P. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development. PLoS ONE. 2013;8:e63218 pubmed publisher
    ..Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development...
  23. Pei D, Luther W, Wang W, Paw B, Stewart R, George R. Distinct neuroblastoma-associated alterations of PHOX2B impair sympathetic neuronal differentiation in zebrafish models. PLoS Genet. 2013;9:e1003533 pubmed publisher
    Heterozygous germline mutations and deletions in PHOX2B, a key regulator of autonomic neuron development, predispose to neuroblastoma, a tumor of the peripheral sympathetic nervous system...
  24. Tu C, Yang T, Huang H, Tsai H. Zebrafish arl6ip1 is required for neural crest development during embryogenesis. PLoS ONE. 2012;7:e32899 pubmed publisher
    ..Although the embryonic expression pattern of ADP ribosylation factor-like 6 interacting protein 1 (Arl6ip1) has been reported, its function in neural crest development is unclear...
  25. Culbertson M, Lewis Z, Nechiporuk A. Chondrogenic and gliogenic subpopulations of neural crest play distinct roles during the assembly of epibranchial ganglia. PLoS ONE. 2011;6:e24443 pubmed publisher
  26. Hines J, Ravanelli A, Schwindt R, Scott E, Appel B. Neuronal activity biases axon selection for myelination in vivo. Nat Neurosci. 2015;18:683-9 pubmed publisher
    ..We propose that axon selection for myelination results from excessive and indiscriminate initiation of wrapping followed by refinement that is biased by activity-dependent secretion from axons. ..
  27. Fortuna V, Pardanaud L, Brunet I, Ola R, Ristori E, Santoro M, et al. Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons. Cell Rep. 2015;11:1786-96 pubmed publisher
    ..Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation. ..
  28. Reichenbach B, Delalande J, Kolmogorova E, Prier A, Nguyen T, Smith C, et al. Endoderm-derived Sonic hedgehog and mesoderm Hand2 expression are required for enteric nervous system development in zebrafish. Dev Biol. 2008;318:52-64 pubmed publisher
    ..Furthermore we show that endoderm and HH signaling, but not hand2, regulate gdnf expression in the intestine, highlighting a central role of endoderm and SHH in patterning the intestine and the ENS. ..
  29. Hockman D, Burns A, Schlosser G, Gates K, Jevans B, Mongera A, et al. Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes. elife. 2017;6: pubmed publisher
  30. Pietsch J, Delalande J, Jakaitis B, Stensby J, Dohle S, Talbot W, et al. lessen encodes a zebrafish trap100 required for enteric nervous system development. Development. 2006;133:395-406 pubmed
    ..These studies demonstrate that lsn/trap100 is not required for initial steps of cranial neural crest development and migration, but is essential for later proliferation of ENS precursors in the intestine. ..
  31. Dupret B, Volkel P, Vennin C, Toillon R, Le Bourhis X, Angrand P. The histone lysine methyltransferase Ezh2 is required for maintenance of the intestine integrity and for caudal fin regeneration in zebrafish. Biochim Biophys Acta Gene Regul Mech. 2017;1860:1079-1093 pubmed publisher
    ..In addition, ezh2-deficient mutants fail to properly regenerate their spinal cord after caudal fin transection suggesting that Ezh2 and H3K27me3 methylation might also be involved in the process of regeneration in zebrafish. ..