2016
DOI: 10.1242/dev.134338
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Minibrain drives the Dacapo dependent cell cycle exit of neurons in the Drosophila brain by promoting asense and prospero expression

Abstract: A key aim of neurodevelopmental research is to understand how precursor cells decide to stop dividing and commence their terminal differentiation at the correct time and place. Here, we show that minibrain (mnb), the Drosophila ortholog of the Down syndrome candidate gene DYRK1A, is transiently expressed in newborn neuronal precursors known as ganglion cells (GCs). Mnb promotes the cell cycle exit of GCs through a dual mechanism that regulates the expression of the cyclin-dependent kinase inhibitor Dacapo, the… Show more

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Cited by 26 publications
(36 citation statements)
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“…Overexpression of DYRK1A inhibits proliferation of tumor cell lines from different tissues (Litovchick et al, 2011) whereas DYRK1A inhibitors such as INDY are mitogenic (Wang et al, 2015), indicating that DYRK1A is a general repressor of mammalian cell proliferation. Reciprocally, loss of function of Drosophila Minibrain/DYRK1A leads to overproliferation of neuronal precursors that fail to differentiate and die by apoptosis, resulting in a small brain (Shaikh et al, 2016). At the molecular level, DYRK1A acts via cell cycle-associated proteins (Fernández-Martinez et al, 2015).…”
Section: Discussionmentioning
confidence: 99%
“…Overexpression of DYRK1A inhibits proliferation of tumor cell lines from different tissues (Litovchick et al, 2011) whereas DYRK1A inhibitors such as INDY are mitogenic (Wang et al, 2015), indicating that DYRK1A is a general repressor of mammalian cell proliferation. Reciprocally, loss of function of Drosophila Minibrain/DYRK1A leads to overproliferation of neuronal precursors that fail to differentiate and die by apoptosis, resulting in a small brain (Shaikh et al, 2016). At the molecular level, DYRK1A acts via cell cycle-associated proteins (Fernández-Martinez et al, 2015).…”
Section: Discussionmentioning
confidence: 99%
“…It is involved in multiple facets of behavior, and mutants have deficits in behaviors including visual learning and memory. The mutant has a morphologically smaller brain when compared to wild-type (Degoutin et al 2013, 1176; Helfrich 1986, 321-343; Shaikh et al 2016, 3195-3205; Tejedor et al 1995, 287-301; Sokolowski 2001, 879). It is GO term enriched in development, nervous system process, behavior, responses to stimuli, and signaling.…”
Section: Resultsmentioning
confidence: 96%
“…Under conditions where TORC1 is inactive, the repression on AtYAK1 is lifted, and AtYAK1 activates plant-specific CDK inhibitors, SMR (Siamese-related) proteins, to negatively regulate cell cycle progression [235]. Yeast YAK1 and its metazoan orthologs, mammalian DYRK1A and fly Minibrain kinases, also have known roles in inhibiting proliferation [236242]. The mammalian DYRK1A upregulates the expression of the gene encoding CDK inhibitor, CDKN1B (also known as p27 KIP1 ) [239].…”
Section: Signaling Network Linking the Metabolic Status To Growth Inmentioning
confidence: 99%