Gene Symbol: Bhlhe22
Description: basic helix-loop-helix family, member e22
Alias: Beta3, Beta3a, Bhlhb5, class E basic helix-loop-helix protein 22, basic helix-loop-helix (bHLH) gene, class B, beta3, basic helix-loop-helix domain containing, class B5, class B basic helix-loop-helix protein 5
Species: mouse
Products:     Bhlhe22

Top Publications

  1. Kim M, Gunnersen J, Augustine C, Tan S. Region-specific expression of the helix-loop-helix gene BETA3 in developing and adult brains. Mech Dev. 2002;114:125-8 pubmed
    ..b>BETA3 is a novel member originally cloned from pancreatic cells but we report here highly restricted expression patterns ..
  2. Xu Z, Dutra A, Stellrecht C, Wu C, Piatigorsky J, Saunders G. Functional and structural characterization of the human gene BHLHB5, encoding a basic helix-loop-helix transcription factor. Genomics. 2002;80:311-8 pubmed
    ..Using both genomic and cDNA mouse and human clones encoding a neural-specific bHLH protein, human BHLHB5 was cloned and mapped to a region on chromosome 8q13 that segregates with Duane syndrome...
  3. Brunelli S, Innocenzi A, Cossu G. Bhlhb5 is expressed in the CNS and sensory organs during mouse embryonic development. Gene Expr Patterns. 2003;3:755-9 pubmed
    ..Here we describe the expression of Bhlhb5, belonging to the beta3 subfamily, in mouse embryos ranging from 9 to 16.5dpc. Bhlhb5 is initially detected at 9...
  4. Liu B, Liu Z, Chen T, Li H, Qiang B, Yuan J, et al. Selective expression of Bhlhb5 in subsets of early-born interneurons and late-born association neurons in the spinal cord. Dev Dyn. 2007;236:829-35 pubmed
    ..In this study, we report a detailed immunological study on the expression of Bhlhb5 in embryonic mouse spinal cord with a newly developed antibody...
  5. Feng L, Xie X, Joshi P, Yang Z, Shibasaki K, Chow R, et al. Requirement for Bhlhb5 in the specification of amacrine and cone bipolar subtypes in mouse retina. Development. 2006;133:4815-25 pubmed
    ..Here, we demonstrate that the expression of Bhlhb5, a bHLH transcription factor of the Olig family, is tightly associated with the generation of selective GABAergic ..
  6. Appler J, Lu C, Druckenbrod N, Yu W, Koundakjian E, Goodrich L. Gata3 is a critical regulator of cochlear wiring. J Neurosci. 2013;33:3679-91 pubmed publisher
    ..As the first auditory-specific regulator of SGN development, Gata3 provides a useful molecular entry point for efforts to engineer SGNs for the restoration of hearing. ..
  7. Ding Q, Chen H, Xie X, Libby R, Tian N, Gan L. BARHL2 differentially regulates the development of retinal amacrine and ganglion neurons. J Neurosci. 2009;29:3992-4003 pubmed publisher
    ..Thus, BARHL2 appears to have numerous roles in retinal development, including regulating neuronal subtype specification, differentiation, and survival. ..
  8. 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
    ..Here, we report that the Olig-related transcription factor Bhlhb5 (also known as Bhlhe22) forms a repressor complex with the PR/SET domain protein, Prdm8...
  9. Ross S, Mardinly A, McCord A, Zurawski J, Cohen S, Jung C, et al. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron. 2010;65:886-98 pubmed publisher
    ..Here we show that the atonal-related transcription factor Bhlhb5 is transiently expressed in the dorsal horn of the developing spinal cord and appears to play a role in the ..

More Information


  1. Qiu F, Jiang H, Xiang M. A comprehensive negative regulatory program controlled by Brn3b to ensure ganglion cell specification from multipotential retinal precursors. J Neurosci. 2008;28:3392-403 pubmed publisher
    ..Our data suggest that Brn3b specifies the RGC fate from multipotential precursors not only by promoting RGC differentiation but also by suppressing non-RGC differentiation programs as a safeguard mechanism. ..
  2. Roberts J, Ennajdaoui H, Edmondson C, Wirth B, Sanford J, Chen B. Splicing factor TRA2B is required for neural progenitor survival. J Comp Neurol. 2014;522:372-92 pubmed publisher
    ..Thus, TRA2B is essential for proper development of the cerebral cortex. ..
  3. Holm P, Mader M, Haubst N, Wizenmann A, Sigvardsson M, Gotz M. Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon. Mol Cell Neurosci. 2007;34:99-119 pubmed
    ..of various transcription factors involved in neurogenesis (like Satb2, Nfia, AP-2gamma, NeuroD6, Ngn2, Tbr2, Bhlhb5) and the retinoic acid signalling molecule Rlbp1 were reduced...
  4. Dennis D, Wilkinson G, Li S, Dixit R, Adnani L, Balakrishnan A, et al. Neurog2 and Ascl1 together regulate a postmitotic derepression circuit to govern laminar fate specification in the murine neocortex. Proc Natl Acad Sci U S A. 2017;114:E4934-E4943 pubmed publisher
    ..Proneural genes thus act in a context-dependent fashion as early determinants, promoting deep-layer neurogenesis in early cortical progenitors via input into the derepression circuit while also influencing other temporal regulators. ..
  5. Harb K, Magrinelli E, Nicolas C, Lukianets N, Frangeul L, Pietri M, et al. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications. elife. 2016;5:e09531 pubmed publisher
  6. Quille M, Carat S, Quémener Redon S, Hirchaud E, Baron D, Benech C, et al. High-throughput analysis of promoter occupancy reveals new targets for Arx, a gene mutated in mental retardation and interneuronopathies. PLoS ONE. 2011;6:e25181 pubmed publisher
    ..Overall, these results identified multiple new candidate targets for Arx and should help to better understand the pathophysiological mechanisms of intellectual disability and epilepsy associated with ARX mutations. ..
  7. Kardon A, Polgár E, Hachisuka J, Snyder L, Cameron D, Savage S, et al. Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord. Neuron. 2014;82:573-86 pubmed publisher
    ..Previous studies revealed that Bhlhb5(-/-) mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological ..
  8. Adnani L, Langevin L, Gautier E, Dixit R, Parsons K, Li S, et al. Zac1 Regulates the Differentiation and Migration of Neocortical Neurons via Pac1. J Neurosci. 2015;35:13430-47 pubmed publisher
    ..Our studies are relevant because loss of 6q24 maternal imprinting in humans results in elevated ZAC1 expression, which has been associated with neurocognitive defects. ..
  9. Liu A, Wang Y, Zhang D, Wang X, Song H, Dang C, et al. Classification and evolutionary analysis of the basic helix-loop-helix gene family in the green anole lizard, Anolis carolinensis. Mol Genet Genomics. 2013;288:365-80 pubmed publisher
    ..Our classification and evolutionary analysis has provided insights into the evolutionary diversification of animal bHLH genes, and should aid future studies on bHLH protein regulation of key growth and developmental processes. ..
  10. Betancourt J, Katzman S, Chen B. Nuclear factor one B regulates neural stem cell differentiation and axonal projection of corticofugal neurons. J Comp Neurol. 2014;522:6-35 pubmed publisher
    ..Together these results demonstrate the critical functions of NFIB in regulating cortical development. ..
  11. Braz J, Juarez Salinas D, Ross S, Basbaum A. Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch. J Clin Invest. 2014;124:3612-6 pubmed publisher
    ..been reported that loss of GABAergic interneurons in mice harboring a deletion of the transcription factor Bhlhb5 generates a severe, nonremitting condition of chronic itch...
  12. Gaber Z, Butler S, Novitch B. PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors. PLoS Biol. 2013;11:e1001676 pubmed publisher
    ..Together, these findings reveal a novel transcriptional strategy for spatially tuning the responsiveness of distinct neural progenitor groups to broadly distributed mitogenic signals in the embryonic environment. ..
  13. Chambers D, Wilson L, Alfonsi F, Hunter E, Saxena U, Blanc E, et al. Rhombomere-specific analysis reveals the repertoire of genetic cues expressed across the developing hindbrain. Neural Dev. 2009;4:6 pubmed publisher
    ..These findings give the first genome-wide insight into the complexity of gene expression during patterning of the developing hindbrain. ..
  14. Pao G, Zhu Q, Perez Garcia C, Chou S, Suh H, Gage F, et al. Role of BRCA1 in brain development. Proc Natl Acad Sci U S A. 2014;111:E1240-8 pubmed publisher
  15. Deans M, Krol A, Abraira V, Copley C, Tucker A, Goodrich L. Control of neuronal morphology by the atypical cadherin Fat3. Neuron. 2011;71:820-32 pubmed publisher
    ..Since complex nervous systems are characterized by the addition of layers, these results demonstrate that mutations in a single gene can cause fundamental changes in circuit organization that may drive nervous system evolution. ..
  16. Feng L, Xie Z, Ding Q, Xie X, Libby R, Gan L. MATH5 controls the acquisition of multiple retinal cell fates. Mol Brain. 2010;3:36 pubmed publisher
    ..This change in cell fate choices is accompanied by an up-regulation of NEUROD1, RXR? and BHLHB5, the transcription factors essential for the differentiation of retinal cells other than RGCs...
  17. Mattar P, Langevin L, Markham K, Klenin N, Shivji S, Zinyk D, et al. Basic helix-loop-helix transcription factors cooperate to specify a cortical projection neuron identity. Mol Cell Biol. 2008;28:1456-69 pubmed
    ..ectopic marker expression in a defined temporal sequence, including early (24 h; Nscl2), intermediate (48 h; BhlhB5), and late (72 h; NeuroD, NeuroD2, Math2, and Tbr1) target genes...
  18. Nelson B, Hartman B, Ray C, Hayashi T, Bermingham McDonogh O, Reh T. Acheate-scute like 1 (Ascl1) is required for normal delta-like (Dll) gene expression and notch signaling during retinal development. Dev Dyn. 2009;238:2163-78 pubmed publisher
    ..Thus, these results suggest a molecular mechanism whereby attenuated Notch levels coupled with reduced proneurogenic activity in progenitors leads to increased gliogenesis and decreased neurogenesis in the Ascl1-deficient retina. ..
  19. Jiang H, Xiang M. Subtype specification of GABAergic amacrine cells by the orphan nuclear receptor Nr4a2/Nurr1. J Neurosci. 2009;29:10449-59 pubmed publisher
  20. Druckenbrod N, Goodrich L. Sequential Retraction Segregates SGN Processes during Target Selection in the Cochlea. J Neurosci. 2015;35:16221-35 pubmed publisher
  21. Shi M, Zheng M, Liu Z, Hu Z, Huang Y, Chen J, et al. DCC is specifically required for the survival of retinal ganglion and displaced amacrine cells in the developing mouse retina. Dev Biol. 2010;348:87-96 pubmed publisher
    ..Thus, our findings suggest that DCC is a key regulator for the survival of specific types of neurons during retinal development and that DCC-P3 domain is essential for this developing event. ..
  22. Georgi S, Reh T. Dicer is required for the maintenance of notch signaling and gliogenic competence during mouse retinal development. Dev Neurobiol. 2011;71:1153-69 pubmed publisher
  23. Ramos C, Rocha S, Gaspar C, Henrique D. Two Notch ligands, Dll1 and Jag1, are differently restricted in their range of action to control neurogenesis in the mammalian spinal cord. PLoS ONE. 2010;5:e15515 pubmed publisher
    ..However, Jag1 can only activate Notch signalling within the V1 and dI6 domains, whereas Dll1 can signal to neural progenitors both inside and outside its domains of expression. ..
  24. Duquette P, Zhou X, Yap N, MacLaren E, Lu J, Wallace V, et al. Loss of LMO4 in the retina leads to reduction of GABAergic amacrine cells and functional deficits. PLoS ONE. 2010;5:e13232 pubmed publisher
    ..We found that these mice have fewer Bhlhb5-positive GABAergic amacrine and OFF-cone bipolar cells...
  25. Das G, Choi Y, Sicinski P, Levine E. Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells. Neural Dev. 2009;4:15 pubmed publisher
  26. Cederquist G, Azim E, Shnider S, Padmanabhan H, Macklis J. Lmo4 establishes rostral motor cortex projection neuron subtype diversity. J Neurosci. 2013;33:6321-32 pubmed publisher
    ..Together, these results identify Lmo4 as a central developmental control over the diversity of motor cortex projection neuron subpopulations, establishing their area-specific identity and specialized connectivity. ..
  27. Cai X, Kardon A, Snyder L, Kuzirian M, Minestro S, de Souza L, et al. Bhlhb5::flpo allele uncovers a requirement for Bhlhb5 for the development of the dorsal cochlear nucleus. Dev Biol. 2016;414:149-60 pubmed publisher
    ..Here, we reveal that Bhlhb5 is expressed in both excitatory (unipolar brush cells) and inhibitory neurons (cartwheel cells) of the DCN during ..
  28. Huang L, Hu F, Feng L, Luo X, Liang G, Zeng X, et al. Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice. Dev Dyn. 2014;243:279-89 pubmed publisher
    b>BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid-releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas...
  29. Srinivasan K, Leone D, Bateson R, Dobreva G, KOHWI Y, Kohwi Shigematsu T, et al. A network of genetic repression and derepression specifies projection fates in the developing neocortex. Proc Natl Acad Sci U S A. 2012;109:19071-8 pubmed publisher
    ..we show that Satb2 and Fezf2 regulate two disease-related genes, Auts2 (Autistic Susceptibility Gene2) and Bhlhb5 (mutated in Hereditary Spastic Paraplegia), providing a molecular handle to investigate circuit disorders in ..
  30. Yu W, Appler J, Kim Y, Nishitani A, Holt J, Goodrich L. A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing. elife. 2013;2:e01341 pubmed publisher
    ..Hence, Mafb is a powerful regulator of cell-type specific features of auditory synaptogenesis that offers a new entry point for treating hearing loss. DOI:
  31. Gray P, Hayes J, Ling G, Llona I, Tupal S, Picardo M, et al. Developmental origin of preBötzinger complex respiratory neurons. J Neurosci. 2010;30:14883-95 pubmed publisher
    ..These data indicate that Dbx1-derived neurons are essential for the expression and, we hypothesize, are responsible for the generation of respiratory behavior both in vitro and in vivo. ..
  32. De Marco García N, Priya R, Tuncdemir S, Fishell G, Karayannis T. Sensory inputs control the integration of neurogliaform interneurons into cortical circuits. Nat Neurosci. 2015;18:393-401 pubmed publisher
  33. Mattar P, Ericson J, Blackshaw S, Cayouette M. A conserved regulatory logic controls temporal identity in mouse neural progenitors. Neuron. 2015;85:497-504 pubmed publisher
    ..These results uncover a conserved strategy regulating temporal identity transitions from flies to mammals. ..
  34. Star E, Zhu M, Shi Z, Liu H, Pashmforoush M, Sauve Y, et al. Regulation of retinal interneuron subtype identity by the Iroquois homeobox gene Irx6. Development. 2012;139:4644-55 pubmed publisher
    ..This work provides insight into the generation of neuronal subtypes by revealing a mechanism in which opposing, yet interdependent, transcription factors regulate subtype identity. ..
  35. Fame R, MacDonald J, Dunwoodie S, Takahashi E, Macklis J. Cited2 Regulates Neocortical Layer II/III Generation and Somatosensory Callosal Projection Neuron Development and Connectivity. J Neurosci. 2016;36:6403-19 pubmed publisher
    ..Gaining insight into molecular development and heterogeneity of CPN will advance understanding of both diverse functions of CPN and of the remarkable range of neurodevelopmental deficits correlated with CPN/CC development. ..
  36. Zembrzycki A, Perez Garcia C, Wang C, Chou S, O Leary D. Postmitotic regulation of sensory area patterning in the mammalian neocortex by Lhx2. Proc Natl Acad Sci U S A. 2015;112:6736-41 pubmed publisher
    ..Our results reemphasize critical roles for Lhx2 that acts as one of the terminal selector genes in controlling principal properties of neurons. ..
  37. Sanosaka T, Namihira M, Asano H, Kohyama J, Aisaki K, Igarashi K, et al. Identification of genes that restrict astrocyte differentiation of midgestational neural precursor cells. Neuroscience. 2008;155:780-8 pubmed publisher
    ..Taken together, our data suggest that astrocyte differentiation of NPCs is regulated not only by DNA methylation but also by genes whose expression is controlled spatio-temporally during brain development. ..
  38. Jin K, Jiang H, Mo Z, Xiang M. Early B-cell factors are required for specifying multiple retinal cell types and subtypes from postmitotic precursors. J Neurosci. 2010;30:11902-16 pubmed publisher
  39. Sigulinsky C, German M, Leung A, Clark A, Yun S, Levine E. Genetic chimeras reveal the autonomy requirements for Vsx2 in embryonic retinal progenitor cells. Neural Dev. 2015;10:12 pubmed publisher
    ..These findings highlight the complexity of Vsx2 function during retinal development and provide a framework for identifying the molecular mechanisms mediating these functions. ..