Disease relevance of Atoh1

• However, 21 genes were specifically up-regulated in medulloblastoma, including sFrp1, Ptc2, and Math1, members of signaling pathways that regulate cerebellar development [1].
• MATH-1 mRNA is first detected in the cranial ganglions and the dorsal part of the central nervous system on embryonic day 9.5 (E9.5) [2].
• Hath1 expression in the HT29 colon cancer cell line can significantly inhibit its proliferation and anchorage-independent growth both in vitro and in vivo [3].
• A Role for Hath1, a bHLH Transcription Factor, in Colon Adenocarcinoma [3].

High impact information on Atoh1

• Requirement of Math1 for secretory cell lineage commitment in the mouse intestine [4].
• We find that loss of Math1 leads to depletion of goblet, enteroendocrine, and Paneth cells without affecting enterocytes [4].
• Math1: an essential gene for the generation of inner ear hair cells [5].
• Embryonic Math1-null mice failed to generate cochlear and vestibular hair cells [5].
• Here, we demonstrate that Gfi1 functions downstream of Math1 in intestinal secretory lineage differentiation [6].

Biological context of Atoh1

• However, Math1-null rhombic lip cells presented conspicuous downregulation of Notch4 and Dll1 [7].
• We also showed that down-regulation of Hes5 and up-regulation of Math1 were associated with ectopic hair cell induction [8].
• Hath1 up-regulates gastric mucin gene expression in gastric cells [9].
• Moreover, knockdown of Hath1 by means of RNA interference significantly decreased the expression of both mucin genes [9].
• We have utilized an in vivo-inducible genetic-fate-mapping strategy to permanently label cohorts of Math1-positive cells and their progeny that arise in the rhombic lip of the cerebellar primordium during embryogenesis [10].

Anatomical context of Atoh1

• The transcription factor Math1 (encoded by the gene Atoh1, also called Math1) is required for the formation of mechanosensory hair cells in the inner ear; however, its specific molecular role is unknown [11].
• It is thought that small intestinal epithelial stem cell progeny, via Notch signaling, yield a Hes1-expressing columnar lineage progenitor and an Atoh1 (also known as Math1)-expressing common progenitor for all granulocytic lineages including enteroendocrine cells, one of the body's largest populations of endocrine cells [12].
• E18.5 Atoh1 null mice have many afferent fibers to the apex of the cochlea, the anterior and the posterior crista, all areas with numerous Bdnf-beta-galactosidase-positive cells [13].
• Absence of Bdnf-beta-galactosidase expression in the utricle and saccule of Atoh1 null mice is first noted at E12.5, a time when Atoh1-beta-galactosidase expression is also first detected in these epithelia [13].
• Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell formation during the development of the organ of Corti [14].

Associations of Atoh1 with chemical compounds

• Math1 Target Genes Are Enriched With Evolutionarily Conserved Clustered E-box Binding Sites [15].

Physical interactions of Atoh1

• Moreover, Math1 bound the Mbh1 enhancer containing the E-box in vivo and activated gene expression [16].

Regulatory relationships of Atoh1

• Therefore, Id proteins are good candidates for regulating Math1 in the cochlea [14].
• The Barhl1 expression has been demonstrated to be induced by the transcription factor Math1 involved in BMP responses [17].
• These results are consistent with the hypothesis that activation of Notch via Jagged2 acts to inhibit expression of Math1 in cochlear progenitor cells, possibly through the activity of HES5 [18].
• Generation of commissural neurons by Math1 was inhibited by a dominant negative form of Mbh1 [16].

Other interactions of Atoh1

• The bHLH-related inhibitors of differentiation and DNA binding (Id) proteins are known to negatively regulate many bHLH transcription factors, including Math1, in a number of different systems [14].
• These results indicate a key role for Ids in the regulation of expression of Math1 and hair cell differentiation in the developing cochlea [14].
• The developmental expression pattern of Fgf14 in the cerebellum is complementary to that of Math1, a marker for proliferating granule cells in the external germinal layer [19].
• Neurotrophins facilitate neuronal differentiation of cultured neural stem cells via induction of mRNA expression of basic helix-loop-helix transcription factors Mash1 and Math1 [20].
• Some of the dorsal Olig3 lineage cells co-expressed Islet1/2, Math1, or Brn3a, markers for dorsal interneuron [21].

Analytical, diagnostic and therapeutic context of Atoh1

• After purification by FACS and coculture with postnatal cerebellar neurons, ES cell-derived Math1+ cells exhibit typical features of neurons of the external granule cell layer, including extensive motility and a T-shaped morphology [22].
• 5. PCR analysis shows expression of Atoh 1 in the otocyst as early as E10.5, prior to any histology-based detection techniques [23].
• A similar expression of Atoh 1-LacZ exists in postnatal and adult vestibular and cochlear sensory neurons, and Atoh 1 expression in vestibular sensory neurons is confirmed with RT-PCR [23].
• Dissection of the cellular and molecular events that position cerebellar Purkinje cells: a study of the math1 null-mutant mouse [24].
• Taken together, we propose that when putative direct targets of Math1 are being selected for detailed studies on DNA microarray hybridization, the enrichment and clustering of binding E-boxes in multiple species may be helpful criteria [15].

References