Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells.

Abstract

Using monoclonal antibodies, we have examined the expression pattern of MASH1, a basic helix-loop-helix protein that is a mammalian homolog of the Drosophila achaete-scute proteins. In Drosophila, achaete-scute genes are required for the determination of a subset of neurons. In the rat embryo, MASH1 expression is confined to subpopulations of neural precursor cells. The induction of MASH1 precedes, but is extinguished upon, overt neuronal differentiation. MASH1 is expressed in the forebrain by spatially restricted domains of neuroepithelium and in the peripheral nervous system exclusively by precursors of sympathetic and enteric neurons. The features of early and transient expression, in spatially restricted subpopulations of neural precursors, are similar to those observed for achaete-scute. Thus, the amino acid sequence conservation between MASHI and achaete-scute is reflected in a parallel conservation of cell type specificity of expression, similar to the case of mammalian MyoD and Drosophila nautilus. These data support the idea that helix-loop-helix proteins may represent an evolutionarily conserved family of cell-type determination genes, of which MASH1 is the first neural-specific member identified in vertebrates.

hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors

“…However, both of these two hASH1 þ adenocarcinomas also expressed neuroendocrine markers. Thus, our data confirmed and extended the findings of previous in vitro studies that hASH1 was specifically expressed in lung cancers with neuroendocrine differentiation, 12,14,18,19 indicating that besides being instrumental in development of a subset of neurons and neuroendocrine cells, 8,[13][14][15][16][17] hASH1 also plays a key role in regulating neuroendocrine differentiation of tumor cells. The term 'neuroendocrine differentiation' in a broad sense is used to define cells expressing a neural and/or an endocrine phenotype.…”

“…Across the spectrum of pulmonary neuroendocrine tumors, typical carcinoid and small-cell carcinoma represent the two ends of the differentiation extent, with atypical carcinoid and large-cell neuroendocrine carcinoma in between. The Drosophila and mammalian homologs of hASH1 are only transiently expressed in neuronal progenitor cells and pulmonary neuroendocrine cells during early fetal development, 8,9,11,13 and in vitro hASH1 expression preceded and overlapped induced neuronal differentiation of neuroblastoma and P19 cells, but vanished before the overt neuronal phenotype appeared. 22,31 Silencing of hASH1 expression also parallelled the development of induced mature C cell phenotype of medullary thyroid carcinoma cells.…”

“…This work was supported by Grants from the Ministry of Education, Culture, Sports, Science and Technology (15590314 and High-tech research center) and from the Ministry of Health, Labor and Welfare (11)(12)(13)(14)(15)(16)(17)(18)(19) 2002), Japan…”

“…11,12 Subsequent studies have documented that MASH1, like its Drosophila homolog, is specifically and transiently expressed in embryonic neuronal precursors and is instrumental in the development of a subset of neurons. 8,13 MASH1 is also indispensable for the development of pulmonary neuroendocrine cells, thyroid C cells and adrenal chromaffin cells in fetal mice, and homozygous MASH1 null mice lack pulmonary neuroendocrine cells, while mice deficient in HES1, a specific repressor gene of hASH1, show a marked increase in pulmonary neuroendocrine cells. [14][15][16][17] In vitro studies also documented restrictive hASH1 expression in tumor cell lines with neuroendocrine or neuronal differentiation such as pulmonary small-cell carcinoma, medullary thyroid carcinoma and neuroblastoma, 12,14,[18][19][20][21][22][23] suggesting a key role for hASH1 in dictating cellular neuroendocrine differentiation in lung cancer.…”

Progenitor cells of the olfactory receptor neuron lineage

“…Mash1 is expressed in subsets of neural progenitors in the central and peripheral nervous systems, including the olfactory epithelium Johnson et al, 1990;Lo et al, 1991). In mice homozygous for targeted disruption of the Mash1 gene, profound reductions in the numbers of several types of neurons, including autonomic, enteric, and olfactory receptor neurons, are observed .…”