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FLASH GENE

Symbol

ASCL1

contributors: mct/npt/pgu - updated : 06-05-2015

HGNC name	achaete-scute complex homolog 1 (Drosophila)
HGNC id	738

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic thymus         Cardiovascular heart         Digestive liver       highly Nervous brain diencephalon hypothalamus     Respiratory lung       highly Visual eye retina       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Epithelial secretory glandular endocrine   Nervous central       Nervous peripherous

cell lineage	present in proliferating progenitor cells but these cells are actively differentiating as evidenced by rapid migration out of germinal zones
cell lines
fluid/secretion

at STAGE

physiological period

embryo

Text	embryonic neuronal precursors of both the peripheral and central nervous systems

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	the N terminus
	one basic helix-loop-helix (HLH) domain
	two domains similar to those in enzymes of the luciferase family
	a long gap region between the similar domains and the C terminus

HOMOLOGY

interspecies	homolog to Drosophila achaete-scute 1
	ortholog to murine Mash1 (90 pc)

Homologene

FAMILY	basic helix-loop-helix (BHLH) family of transcription factors
	long-chain fatty-acid-coenzyme A ligase family
	ATP-dependent AMP-binding enzyme family

CATEGORY

enzyme , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	playing a role in the neuronal commitment and differentiation and in the generation of olfactory and autonomic neurons
	converting free long-chain fatty acids into fatty acyl-CoA esters
	playing a role in lipid brosynthesis and fatty acid degradation
	using preferentially oleate, arachidonate, eicosapentaenoate and docosahexaenoate as substrates
	involved in the formation of the neuronal network for autonomous control of ventilation
	proneural basic helix-loop-helix (bHLH) transcription factors not only initiating neuronal differentiation but also potentiating cell migration
	promote branchiomotor neuron development but also regulate the subsequent oligodendrocyte development and the cytoarchitecture by maintaining neural progenitors through Notch signaling
	required for normal development of POMC(+) neurons and both required for the generation of ventral neuroendocrine neurons as well as playing a central role in subtype specification of these neurons
	controls development of the locus coeruleus
	proneural basic helix–loop–helix transcriptional factor that plays an essential role during neuronal specification of precursor cells
	bHLH transcription factor essential for neuronal differentiation and specification in the nervous system
	required for normal development of the nervous system and has been implicated in the formation of neuroendocrine tumors
	NEUROG2 and ASCL1 regulate the temporal progression of retinal neurogenesis by directing overlapping waves of neuron formation
	required for neurogenesis and neuronal subtype specification in the ventral hypothalamus
	ASCL1 lineage cells contribute to stroke-induced neurogenesis and oligodendrogenesis in the adult ischemic brain
	its expression defines a competence-restricted progenitor lineage in the retina, providing a new mechanism to explain fate diversification
	plays a specific role during the time period when Pcs (Purkinje cells) are generated in restricting ventricular zone progenitors from becoming rhombic lip progenitors
	combined activity of two distinct BHLH factors (ASCL1 and HELT) plays likely a key role in the development of discrete classes of thalamic interneurons
	ASCL1 and HELT factors cooperate synergistically in midbrain GABAergic neurogenesis

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

digestion

PATHWAY

metabolism

lipid/lipoprotein

signaling

lipid metabolism

a component

INTERACTION

DNA

RNA

small molecule	metal binding, cofactor,
	Mg2+
	AMP

protein	interacts with UBQLN1
	downstream target of FMR1 (improved translation efficiency of ASCL1 mRNA by FMR1 may represent an important regulatory switch in neuronal differentiation)
	GADD45G is a direct transcriptional target of ASCL1
	HAND2 can activate the sympathetic nervous system (SNS) differentiation program by induction of SNS-related genes, including PHOX2B, ASCL1, DBH and TH
	transcriptional complex of LMO3 and NHLH2 may contribute to the genesis and malignant phenotype of neuroblastoma by inhibiting HES1 which suppresses the transactivation of ASCL1
	overexpression of DMRTA1 induced the expression of the proneural gene Neurogenin2 (NEUROG2) and conversely repressed ASCL1, a proneural gene expressed in the ventral telencephalon
	inhibits ASCL1-dependent neurogenesis in neural progenitor cells (NPCs) and direct neuronal conversion in fibroblasts
	GABAergic inducing activity of ASCL1 requires the direct transcriptional regulation of PTF1A, providing therefore a new piece of the network governing neurotransmitter subtype specification during retinogenesis

cell & other

REGULATION

inhibited by

NEUROG2 and ASCL1 are inhibited by CBFA2T2 and CBFA2T3, and less efficiently by RUNX1T1

Other

downregulated in differentiating neuroblastoma cells

ASSOCIATED DISORDERS

corresponding disease(s)

CCHS4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in differentiating neuroblastoma cells tumoral     --over   in a majority of neuroblastoma tumors and cell lines tumoral     --over   in progressive astrocytoma in 85.71 p100 of grade II diffuse astrocytoma, 90 p100 of grade III anaplastic astrocytoma tumoral     --over   87.5 p100 of secondary glioblastoma multiforme constitutional         results in hypoplasia of both the arcuate and ventromedial nuclei tumoral     --other   constitutive expression in lung epithelium promotes remodeling through multiple pathways that are commonly activated during lung carcinogenesis

Susceptibility

to Parkinson disease (in association with PHOX2B)

Variant & Polymorphism repeat	polyglutamine length variant with 13 repeats may exert a protective role for Parkinson disease in a Caucasian population

Candidate gene	for congenital hypoventilation syndrome (CCHS4) or modifier of PHOX2B
Marker
Therapy target

ANIMAL & CELL MODELS

	In Mash1-deficient mice, defects in thalamocortical axon pathfinding were found to be correlated with altered cell domain
	mice lacking Ascl1 in the cerebellum have a major decrease in three types of interneurons with a tendency toward a loss of later-born interneurons, as well as an imbalance of oligodendrocytes and astrocytes