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Gene Review

Ascl1  -  achaete-scute complex homolog 1 (Drosophila)

Mus musculus

Synonyms: AI225900, ASH-1, ASH1, Achaete-scute homolog 1, Ash1, ...
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Disease relevance of Ascl1


High impact information on Ascl1


Chemical compound and disease context of Ascl1

  • We analyzed ventilatory responses to hypercapnia (8% CO2, 21% O2, 71% N2) and hypoxia (10% O2, 3% CO2, 87% N2) in newborn and adult Mash-1 heterozygous mice (Mash-1+/-) and their wild-type littermates (Mash-1+/+) [3].
  • In this study, we found that neural differentiation of multipotent mouse P19 embryonal carcinoma cells by retinoic acid led to the appearance of Scrt together with neuron-specific class III beta-tubulin (Tuj1), following the earlier elaboration of Mash1 [8].

Biological context of Ascl1

  • Thus Ascl1, which is essential for noradrenergic differentiation, is also a determinant of the serotonergic phenotype [9].
  • These results indicate that Mash1 enhances survival of the C-cell progenitors by inhibiting apoptosis [10].
  • While the formation and migration of the ultimobranchial body were not affected in the Mash1 null mutants, at E 12.5-E 13.5 both the ultimobranchial body located close to the arteries and the organ populating the thyroid lobe exhibited a marked increase in apoptotic cell numbers [10].
  • 5. Targeted disruption of Mash1 resulted in the absence of C cells in the mouse thyroid glands, since cells displaying the C-cell markers and expressing NeuroD were not detected during fetal development or at birth [10].
  • Previous analysis of mutant mice has revealed that the bHLH genes Mash1 and Math3, and the homeobox gene Chx10 are essential for generation of bipolar cells, the interneurons present in the inner nuclear layer of the retina [11].

Anatomical context of Ascl1


Associations of Ascl1 with chemical compounds

  • The basic helix-loop-helix (bHLH) gene Ascl1 (also known as Mash1) is coexpressed with Nkx2-2 in the neuroepithelial domain of the hindbrain, which gives rise to 5-HT neurons [9].
  • In the presence of RA, exogenous expression of the sense mRNA caused the intense and rapid induction of neurogenic Brn-2 and Mash-1 mRNA expressions accompanying the strong downregulation of Oct-3/4 mRNA expression, and stimulated both neuronal and glial cell differentiations of P19 cells [16].

Physical interactions of Ascl1

  • We discuss the nonredundancy of Phox2 genes and their complex partnership with the bHLH transcription factor Mash1, which is also required for the differentiation of most noradrenergic cell types [17].

Regulatory relationships of Ascl1

  • However, at later developmental times, Ascl1 controls the expression of Ptf1a in dIL(A) progenitors to promote inhibitory neuron differentiation while at the same time upregulating Notch signaling to ensure the proper generation of dIL(B) excitatory neurons [12].
  • Together, our results suggest that Hes1 regulates Mash1 transcription in the olfactory placode in two different contexts, initially as a prepattern gene defining the placodal domain undergoing neurogenesis and, subsequently, as a neurogenic gene controlling the density of neural progenitors in this domain [13].
  • During the early phase of neurogenesis, Gsh1/2 and Ascl1 coordinately regulate the expression of Tlx3, which is a critical postmitotic determinant for dorsal glutamatergic sensory interneurons [12].
  • Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors [18].
  • Enteric tyrosine hydroxylase-containing cells co-express Mash-1 and are eliminated by the Mash-1-/- mutation, consistent with the idea that in the mouse, as in the rat, these precursors generate serotonergic neurons [19].
  • In agreement with this result, overexpression of cyclin D2 suppressed the anti-proliferative activity of Mash1 [20].

Other interactions of Ascl1

  • Although Mash1 normally has no detectable function in dopaminergic neuron development, it could partially rescue the generation of dopaminergic neuron precursors in the absence of Ngn2 [21].
  • Loss of Hes1 function leads both to expression of Mash1 outside of the normal domain of neurogenesis and to increased density of MASH1-positive progenitors within this domain, and results in an excess of neurons after a delay [13].
  • In its absence, neurogenins are lost from the cortical germinal zone and Gsh2, Mash1 and Dlx genes are found ectopically [22].
  • Gsh2 gene function was found to be essential to maintain the molecular identity of early striatal progenitors and in its absence the ventral telencephalic regulatory genes Mash1 and Dlx are lost from most of the striatal germinal zone [22].
  • Most adrenal medullary cells in Mash1(-/-) mice identified by Phox2b immunoreactivity, lack the catecholaminergic marker tyrosine hydroxylase [15].

Analytical, diagnostic and therapeutic context of Ascl1

  • In this article, we analyse the expression of Mash-1 from its onset during neurulation to adult stages by RNA in situ hybridization on whole mounts and sections [23].
  • RT-PCR revealed that two basic helix-loop-helix (bHLH) genes, Mash-1 and Ngn-1, were up-regulated during the differentiation stage of Wnt-1-overexpressing P19 cells [24].
  • Clonal analysis in culture and transplantation experiments in postnatal brain demonstrate that this phenotype reflects a cell-autonomous function of Mash1 in specification of these two lineages [25].
  • Furthermore, coexpression of Heslike and Mash1 significantly promotes formation of GABAergic neurons, compared with each gene alone, in neural precursor cell culture [26].


  1. ASH1 gene is a specific therapeutic target for lung cancers with neuroendocrine features. Osada, H., Tatematsu, Y., Yatabe, Y., Horio, Y., Takahashi, T. Cancer Res. (2005) [Pubmed]
  2. Requirement of multiple basic helix-loop-helix genes for retinal neuronal subtype specification. Akagi, T., Inoue, T., Miyoshi, G., Bessho, Y., Takahashi, M., Lee, J.E., Guillemot, F., Kageyama, R. J. Biol. Chem. (2004) [Pubmed]
  3. Ventilatory responses to hypercapnia and hypoxia in Mash-1 heterozygous newborn and adult mice. Dauger, S., Renolleau, S., Vardon, G., Népote, V., Mas, C., Simonneau, M., Gaultier, C., Gallego, J. Pediatr. Res. (1999) [Pubmed]
  4. Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons. Guillemot, F., Lo, L.C., Johnson, J.E., Auerbach, A., Anderson, D.J., Joyner, A.L. Cell (1993) [Pubmed]
  5. The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Pattyn, A., Morin, X., Cremer, H., Goridis, C., Brunet, J.F. Nature (1999) [Pubmed]
  6. Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1. Qian, Y., Shirasawa, S., Chen, C.L., Cheng, L., Ma, Q. Genes Dev. (2002) [Pubmed]
  7. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Fode, C., Ma, Q., Casarosa, S., Ang, S.L., Anderson, D.J., Guillemot, F. Genes Dev. (2000) [Pubmed]
  8. Mammalian Scratch participates in neuronal differentiation in P19 embryonal carcinoma cells. Nakakura, E.K., Watkins, D.N., Sriuranpong, V., Borges, M.W., Nelkin, B.D., Ball, D.W. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  9. Ascl1/Mash1 is required for the development of central serotonergic neurons. Pattyn, A., Simplicio, N., van Doorninck, J.H., Goridis, C., Guillemot, F., Brunet, J.F. Nat. Neurosci. (2004) [Pubmed]
  10. Mash1 regulates the development of C cells in mouse thyroid glands. Kameda, Y., Nishimaki, T., Miura, M., Jiang, S.X., Guillemot, F. Dev. Dyn. (2007) [Pubmed]
  11. Roles of homeobox and bHLH genes in specification of a retinal cell type. Hatakeyama, J., Tomita, K., Inoue, T., Kageyama, R. Development (2001) [Pubmed]
  12. Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons. Mizuguchi, R., Kriks, S., Cordes, R., Gossler, A., Ma, Q., Goulding, M. Nat. Neurosci. (2006) [Pubmed]
  13. Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. Cau, E., Gradwohl, G., Casarosa, S., Kageyama, R., Guillemot, F. Development (2000) [Pubmed]
  14. Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons. Helms, A.W., Battiste, J., Henke, R.M., Nakada, Y., Simplicio, N., Guillemot, F., Johnson, J.E. Development (2005) [Pubmed]
  15. Development of chromaffin cells depends on MASH1 function. Huber, K., Brühl, B., Guillemot, F., Olson, E.N., Ernsberger, U., Unsicker, K. Development (2002) [Pubmed]
  16. Implication of Trip15/CSN2 in early stage of neuronal differentiation of P19 embryonal carcinoma cells. Akiyama, H., Sugiyama, A., Uzawa, K., Fujisawa, N., Tashiro, Y., Tashiro, F. Brain Res. Dev. Brain Res. (2003) [Pubmed]
  17. Specification of the central noradrenergic phenotype by the homeobox gene Phox2b. Pattyn, A., Goridis, C., Brunet, J.F. Mol. Cell. Neurosci. (2000) [Pubmed]
  18. Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors. Cau, E., Gradwohl, G., Fode, C., Guillemot, F. Development (1997) [Pubmed]
  19. Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1-dependence. Blaugrund, E., Pham, T.D., Tennyson, V.M., Lo, L., Sommer, L., Anderson, D.J., Gershon, M.D. Development (1996) [Pubmed]
  20. Expression of the proneural gene encoding Mash1 suppresses MYCN mitotic activity. Alvarez-Rodríguez, R., Pons, S. J. Cell. Sci. (2009) [Pubmed]
  21. Neurogenin 2 is required for the development of ventral midbrain dopaminergic neurons. Kele, J., Simplicio, N., Ferri, A.L., Mira, H., Guillemot, F., Arenas, E., Ang, S.L. Development (2006) [Pubmed]
  22. Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2. Toresson, H., Potter, S.S., Campbell, K. Development (2000) [Pubmed]
  23. Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system. Guillemot, F., Joyner, A.L. Mech. Dev. (1993) [Pubmed]
  24. Wnt-1 promotes neuronal differentiation and inhibits gliogenesis in P19 cells. Tang, K., Yang, J., Gao, X., Wang, C., Liu, L., Kitani, H., Atsumi, T., Jing, N. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  25. Mash1 specifies neurons and oligodendrocytes in the postnatal brain. Parras, C.M., Galli, R., Britz, O., Soares, S., Galichet, C., Battiste, J., Johnson, J.E., Nakafuku, M., Vescovi, A., Guillemot, F. EMBO J. (2004) [Pubmed]
  26. Identification of a novel basic helix-loop-helix gene, Heslike, and its role in GABAergic neurogenesis. Miyoshi, G., Bessho, Y., Yamada, S., Kageyama, R. J. Neurosci. (2004) [Pubmed]
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