HATH1
- Known as:
- HATH1
- Catalog number:
- 000535A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- HATH1
Related genes to: HATH1
- Gene:
- ATOH1 NIH gene
- Name:
- atonal bHLH transcription factor 1
- Previous symbol:
- -
- Synonyms:
- HATH1, MATH-1, Math1, bHLHa14
- Chromosome:
- 4q22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1997-02-27
- Date modifiied:
- 2016-10-05
Related products to: HATH1
Related articles to: HATH1
- With its limited diversity of neuronal types and stereotyped cellular organisation, the cerebellum is an excellent model for complex brain development. It exemplifies how simple patterning rules can give rise to complex neural circuits. The entirety of populations of excitatory and inhibitory neurons is characterised by the transient expression of either Atonal1 (Atoh1) or Ptf1a, respectively, and derived from a spatially defined population of Sox2-positive precursors. We present a model where the decision to make Atoh1 over Ptf1a lineage neurons is dictated by inductive cell-cell interactions at the posterior boundary with non-neural roof plate cells at the rhombic lip. The type of Atoh1+ve or Ptf1a+ve cell generated is dictated by a shared temporal code invested in the Sox2-expressing progenitor pool in the ventricular zone of dorsal rhombomere 1. An additional long-lived pool of Sox2 progenitors in the prospective white matter gives rise to glial cells (astrocytes) and later born interneurons, the latter of which also transiently express Ptf1a. Temporal patterning of progenitors generates neuronal diversity and offers a potent substrate for adaptation. In particular, fine-grained temporal patterning of progenitors feeding early rhombic lip derivatives dictates the connections of the cerebellum through specifying cerebellar nucleus output neurons which influence the scaling of the cortex of the cerebellum. In the human cerebellum, scaling involves species-specific adaptations that co-evolved within the human cerebral cortex. - Source: PubMed
Publication date: 2026/02/14
Butts ThomasWingate Richard James T - Lmx1a/b paralogous genes, which arose from the invertebrate Lmx1b-like gene, are critical for hearing in multiple vertebrate species, and mutations in these genes cause hearing deficits in humans. While the unique and redundant functions of Lmx1a/b in the inner ear are well established, their contribution to the development of the cochlear nuclei, which process and relay auditory information to the brain, is poorly understood. Since cochlear nuclei maturate postnatally, here we analyzed Lmx1a;Lmx1b, Lmx1a, and Lmx1a;Lmx1b mice that survive past birth. Loss of Lmx1a reduced distinct populations of excitatory neurons in dorsal (DCN) and ventral (VCN) cochlear nuclei and their innervation from the inner ear. Additional loss of one Lmx1b copy made Lmx1a phenotypes more severe, revealing that Lmx1b acts redundantly with Lmx1a. Unlike Lmx1a mice, excitatory neurons were not affected in Lmx1a;Lmx1b mice. Thus, while cochlear nuclei are sensitive to Lmx1a/b gene dosage, these genes are not completely equivalent, and Lmx1a has a more profound role in cochlear nuclei development. Lmx1a and especially Lmx1a;Lmx1b embryos had fewer Atoh1+ progenitors that produce excitatory neurons of the cochlear nuclei, and reduced Bmp6 expression in the roof plate, the signaling center that induces these progenitors via Bmp signaling. We found that Lmx1a is the primary regulator of Bmp6, whereas Lmx1b contributes only in the absence of Lmx1a. Thus, Lmx1a plays a major role in the formation of the mature structure and connectivity of both the DCV and VCN, and Lmx1b acts redundantly to Lmx1a but only partially compensates for Lmx1a loss. - Source: PubMed
Publication date: 2026/04/17
Iskusnykh Igor YFritzsch BerndYamoah Ebenezer NSteshina Ekaterina YChizhikov Victor V - BackgroundCDX2 is a transcription factor critical for intestinal development and differentiation. While its prognostic value is established in colorectal cancer, its significance in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Given the overlap of intestinal-type features in intraductal papillary mucinous neoplasms (IPMNs), clarifying the role of CDX2 in PDAC and IPMN may provide insights into tumor biology and prognostic markers.MethodsWe retrospectively analyzed 35 PDAC and 42 IPMN-associated carcinoma (IPMC) resected lesions. Immunohistochemistry for CDX2 and intestinal differentiation markers (ATOH1, MUC2, GPA33) was performed. CDX2 expression was semi-quantified using an H-score derived from whole-slide image analysis with QuPath. Associations between CDX2 expression and disease-free survival (DFS) were assessed using Kaplan-Meier and Cox regression analyses.ResultsCDX2 expression was observed in 43% of PDAC and 50% of IPMC. In IPMC, CDX2 positivity was often accompanied by downstream markers, suggesting preserved intestinal-type differentiation. In contrast, CDX2-positive PDAC rarely expressed GPA33 or MUC2, indicating divergence from the intestinal cascade. Higher CDX2 H-scores were significantly associated with lower recurrence ( = .027). ROC analysis showed fair predictive ability with an AUC of 0.74 ( = .008). Although multivariate analysis was not significant, subgroup analysis showed that in PDAC with lymph node metastasis, high CDX2 expression was associated with longer DFS ( = .014).ConclusionsDigitally quantified CDX2 expression may serve as a favorable prognostic biomarker in PDAC, distinct from its role in maintaining intestinal-type differentiation in IPMN. Validation in larger, multicenter cohorts is warranted. - Source: PubMed
Publication date: 2026/04/07
Endo MasatoNiisato YusukeShimomura OsamuSakamoto NoriakiSugita ShoheiHagiwara YuyaFukuda SomaMatsubara DaisukeOda TatsuyaTsuchiya Kiichiro - The limited regenerative capacity of vestibular hair cells (HCs) in mammals is one of the causes of permanent balance disorders. The transcription factor Atoh1 has been identified as a potential candidate for inducing HC regeneration. However, regulation of Atoh1 alone has proven insufficient to achieve functional recovery of the mammalian vestibule. Elucidating the mechanisms underlying Atoh1-induced regeneration may therefore inform strategies to enhance its therapeutic efficacy. Endogenous Sox2 is required for Atoh1-associated HC formation during embryonic development, yet its role in Atoh1 overexpression-induced HC formation after birth remains unclear. In this study, we conditionally knocked down Sox2 while overexpressing Atoh1 in the utricle of neonatal mice or in diphtheria-toxin-injured adult mice. Atoh1 overexpression stimulated supporting cell proliferation and new HC formation in neonates; however, concomitant Sox2 knockdown attenuated the effects. In the diphtheria-toxin-injured adult utricle, Sox2 downregulation similarly weakened Atoh1-induced HC regeneration. These findings demonstrate that endogenous Sox2 expression is essential for Atoh1-induced HC addition and regeneration in the mouse utricle. - Source: PubMed
Publication date: 2026/03/31
Yang Yu-TongGuo Jing-YingXu Jun-YiSu WeiHao Ming-YuZhang TingGong Shu-ShengWang Guo-Peng - Organ development and function are orchestrated by intricate transcriptional circuits. Here, we present a comprehensive atlas profiling 1,904 transcription regulators in the brain, cerebellum, heart, kidney, liver, ovary, and testis of fetal, neonatal, and adult mice. Using this dataset, we uncover Thymocyte Selection-Associated High Mobility Group Box Family Member 3 (TOX3) as a potential coactivator of Atoh1 in cerebellar granule neuron progenitors (GNPs). -deficient mice display severe ataxia and cerebellar hypoplasia, driven by depletion of GNPs, diminished expression, and impaired primary cilia. Single-nucleus RNA-sequencing analyses reveals compromised maintenance of the progenitor pool. is also highly expressed in subsets of medulloblastoma, and its deletion reduces cerebellar neoplasia and prolongs survival in a mouse model. Mechanistically, how lineage-defining factors such as Atoh1 drive robust gene expression despite weak intrinsic transactivation activity remains unclear. We show that Tox3 physically associates with Atoh1 and co-occupies shared regulatory elements, converting an otherwise weak single-copy Atoh1-responsive E-box into a highly active enhancer that drives transcriptional activation by up to 120-fold, including at an ultraconserved E-box downstream of itself. Cross-species single-cell comparisons further show an association between expression and cerebellum expansion during vertebrate evolution. Together, this work supports Tox3 as a critical Atoh1 coactivator in cerebellar development, tumorigenesis, and evolution, while providing an atlas and screening strategy as a valuable resource for exploring novel transcriptional regulators in organogenesis and tissue physiology. - Source: PubMed
Publication date: 2026/03/18
Chen XiaoxinZhong XiaochenYue WilliamWang BruceWoo BrianGoodarzi HaniLuo ZailiLu Q RichardFlamant FrédéricReiter Jeremy FHuang Guo N