Baboon/dSmad2 TGF-β signaling is required during late larval stage for development of adult-specific neurons

Zheng, Xiaoyan; Zugates, Christopher T.; Lu, Zouyan; Shi, Lijun; Bai, Jia-Min; Lee, Tzumin

doi:10.1038/sj.emboj.7600962

Cited by 54 publications

(53 citation statements)

References 51 publications

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“…TGF-␤ knock-out mice show prominent neuronal cell death together with reduced synaptic density in various parts of the brain (Brionne et al, 2003). TGF-␤ signaling regulates axon guidance in Caenorhabditis elegans and is required for synaptic growth, neurotransmitter release, and neuron morphogenesis in Drosophila (Colavita et al, 1998;Zheng et al, 2006). These observations suggest that an impaired TGF-␤ signaling leads to neuron damage.…”

Section: Introductionmentioning

confidence: 79%

Disrupted Transforming Growth Factor-β Signaling in Spinal and Bulbar Muscular Atrophy

Katsuno¹,

Adachi²,

Minamiyama³

et al. 2010

J. Neurosci.

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Spinal and bulbar muscular atrophy (SBMA) is a late-onset lower motor neuron disease caused by the expansion of a trinucleotide CAG repeat, which encodes a polyglutamine tract in androgen receptor (AR). Although it is commonly held that the pathogenic polyglutamine proteins accumulate in neurons and thereby induce transcriptional dysregulation, the downstream molecular events have remained elusive. Here, we examined whether TGF-␤ signaling is dysregulated in SBMA. Nuclear translocation of phosphorylated Smad2/3, a key step in TGF-␤ signaling, is suppressed in the spinal motor neurons of male transgenic mice carrying the mutant human AR. A similar finding was also observed in the motor neurons, but not in Purkinje cells, of SBMA patients. The pathogenic AR, the causative protein of SBMA, inhibits the transcription of TGF-␤ receptor type II (T␤RII) via abnormal interactions with NF-Y and p300/CBP-associated factor. Furthermore, overexpression of T␤RII dampens polyglutamine-induced cytotoxicity in a neuroblastoma cell line expressing the pathogenic AR. The present study thus indicates that disruption of TGF-␤ due to the transcriptional dysregulation of T␤RII is associated with polyglutamine-induced motor neuron damage in SBMA.

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Section: Introductionmentioning

confidence: 79%

Disrupted Transforming Growth Factor-β Signaling in Spinal and Bulbar Muscular Atrophy

Katsuno¹,

Adachi²,

Minamiyama³

et al. 2010

J. Neurosci.

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“…In mushroom body γ neurons, Activin potentiates axonal pruning by promoting the expression of EcR-B1 (Zheng et al, 2003). A similar molecular function for Activin was identified in dorsal cluster neurons, where it was suggested that Activin is required to modulate the rate of neuronal terminal differentiation (Zheng et al, 2006). In the ovary, Activin interacts with the ecdysone pathway at the level of the target gene br-Z1.…”

Section: Different Modes Of Interaction Between the Ecdysone And Actimentioning

confidence: 92%

“…The Activin and ecdysone pathways have previously been shown to associate in the nervous system and in the prothoracic gland (Gibbens et al, 2011;Zheng et al, 2003Zheng et al, , 2006. Interestingly, in each case, the Activin pathway serves to potentiate the function of ecdysone, and in each case Activin affects the ecdysone response at a different level.…”

Section: Different Modes Of Interaction Between the Ecdysone And Actimentioning

confidence: 99%

Activin signaling balances proliferation and differentiation of ovarian niche precursors and enables adjustment of niche numbers

2015

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How the numbers of niches and resident stem cells within a particular organ are determined during development and how they may be modulated or corrected is a question with significant medical implications. In the larval ovary of Drosophila melanogaster, somatic precursors for niches, and germ cells that will become germline stem cells, co-develop. Somatic precursors proliferate during the first 3 days of larval development. By mid-third instar, adult terminal filament (TF) ( part of the germline stem cell niche) cells first appear, and differentiation terminates 24 h later when 16-20 TFs fully form. The developmental sequence responsible for TF cell determination and final TF numbers is only partially understood. We show that TF formation proceeds through several, hitherto uncharacterized stages, which include an early exit from the cell cycle to form TF precursors and two steps of cell shape change to form the mature TF cells. The Activin receptor Baboon (Babo) is required for somatic precursor cell proliferation and therefore determines the pool of TF precursors available for TF differentiation. During the final differentiation stage, Babo facilitates TF and germ cell differentiation, and promotes the accumulation of Broad-Z1, which is also a target of the steroid hormone ecdysone. Epistasis analysis shows that Activin controls cell proliferation in an ecdysone-independent manner and TF differentiation by affecting ecdysone targets. We propose that this mode of function allows Activin to balance proliferation and differentiation, and to equilibrate niche numbers. These results suggest a novel model for how niche numbers are corrected during development.

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“…7A). EB axons normally grow to reach the midline and then extend ventrally to form a closed ring, which is completed by 48 hours PPF (Zheng et al, 2006) (Fig. 7B, n=15).…”

Section: Ptpmeg Protein Is Expressed By Neurons In the Developing Andmentioning

confidence: 99%

Ptpmeg is required for the proper establishment and maintenance of axon projections in the central brain ofDrosophila

et al. 2007

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Ptpmeg is a cytoplasmic tyrosine phosphatase containing FERM and PDZ domains. Drosophila Ptpmeg and its vertebrate homologs PTPN3 and PTPN4 are expressed in the nervous system, but their developmental functions have been unknown. We found that ptpmeg is involved in neuronal circuit formation in the Drosophila central brain, regulating both the establishment and the stabilization of axonal projection patterns. In ptpmeg mutants, mushroom body (MB) axon branches are elaborated normally, but the projection patterns in many hemispheres become progressively abnormal as the animals reach adulthood. The two branches of MB ␣/␤ neurons are affected by ptpmeg in different ways; ptpmeg activity inhibits ␣ lobe branch retraction while preventing ␤ lobe branch overextension. The phosphatase activity of Ptpmeg is essential for both ␣ and ␤ lobe formation, but the FERM domain is required only for preventing ␣ lobe retraction, suggesting that Ptpmeg has distinct roles in regulating the formation of ␣ and ␤ lobes. ptpmeg is also important for the formation of the ellipsoid body (EB), where it influences the pathfinding of EB axons. ptpmeg function in neurons is sufficient to support normal wiring of both the EB and MB. However, ptpmeg does not act in either MB or EB neurons, implicating ptpmeg in the regulation of cell-cell signaling events that control the behavior of these axons.

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Baboon/dSmad2 TGF-β signaling is required during late larval stage for development of adult-specific neurons

Cited by 54 publications

References 51 publications

Disrupted Transforming Growth Factor-β Signaling in Spinal and Bulbar Muscular Atrophy

Disrupted Transforming Growth Factor-β Signaling in Spinal and Bulbar Muscular Atrophy

Activin signaling balances proliferation and differentiation of ovarian niche precursors and enables adjustment of niche numbers

Ptpmeg is required for the proper establishment and maintenance of axon projections in the central brain ofDrosophila

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