Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup

Cowley, Michael; Garfield, Alastair S.; Madon-Simon, Marta; Charalambous, Marika; Clarkson, Richard W. E.; Smalley, Matthew J.; Kendrick, Howard; Isles, Anthony R; Parry, Aled; Carney, Sara; Oakey, Rebecca J.; Heisler, Lora K.; Moorwood, Kim; Wolf, Jason B.; Ward, Andrew

doi:10.1371/journal.pbio.1001799

Cited by 48 publications

(71 citation statements)

References 48 publications

(90 reference statements)

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“…It is also likely that yet to be identified regulatory elements are involved in Grb10 expression. Recent work, for example, identified a downstream putative enhancer element that is critical for paternal expression in brain compared with the spinal cord (46). Further functional experiments that define regulatory regions in the locus are essential to elucidate the mechanisms that control Grb10 expression.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

“…Grb10 mutant mice fed a high-fat diet had greatly increased fat stores compared with their WT littermates. Strikingly, the proportion of lean to fat body mass in Grb10 mutant mice has also recently been shown to be dependent on Grb10 expression in both the mother and the pup (46). Grb10-deficient mothers had a larger effect on adiposity in the pup whereas the genotype of the pup was more strongly associated with influencing its own lean mass.…”

Section: Grb10 Is a Negative Regulator Of Growthmentioning

confidence: 98%

See 1 more Smart Citation

Tissue-specific regulation and function of Grb10 during growth and neuronal commitment

Plasschaert

Bartolomei

2014

Proc. Natl. Acad. Sci. U.S.A.

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Growth-factor receptor bound protein 10 (Grb10) is a signal adapter protein encoded by an imprinted gene that has roles in growth control, cellular proliferation, and insulin signaling. Additionally, Grb10 is critical for the normal behavior of the adult mouse. These functions are paralleled by Grb10’s unique tissue-specific imprinted expression; the paternal copy of Grb10 is expressed in a subset of neurons whereas the maternal copy is expressed in most other adult tissues in the mouse. The mechanism that underlies this switch between maternal and paternal expression is still unclear, as is the role for paternally expressed Grb10 in neurons. Here, we review recent work and present complementary data that contribute to the understanding of Grb10 gene regulation and function, with specific emphasis on growth and neuronal development. Additionally, we show that in vitro differentiation of mouse embryonic stem cells into alpha motor neurons recapitulates the switch from maternal to paternal expression observed during neuronal development in vivo. We postulate that this switch in allele-specific expression is related to the functional role of Grb10 in motor neurons and other neuronal tissues.

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Section: Discussion and Future Directionsmentioning

confidence: 99%

Section: Grb10 Is a Negative Regulator Of Growthmentioning

confidence: 98%

Tissue-specific regulation and function of Grb10 during growth and neuronal commitment

Plasschaert

Bartolomei

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Matching (or mismatching) the offspring’s expressed allele with its mother’s allele in pleiotropic loci affecting both maternal and offspring traits benefits their interaction. This view is supported by maternal Grb10 expression, which in pups reduces nutrient demand and in mammary glands of lactating mothers enhances milk supply, thereby achieving an optimal effect on pup growth (Cowley et al 2014). This theory, however, rationalizes the function of a limited set of imprinted genes, some of which are also explained by the kinship theory (Úbeda & Gardner 2015).…”

Section: Introductionmentioning

confidence: 99%

New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain

Pérez

Rubinstein²,

Dulac

2016

Annu. Rev. Neurosci.

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Mammalian evolution entailed multiple innovations in gene regulation, including the emergence of genomic imprinting, an epigenetic regulation leading to the preferential expression of a gene from its maternal or paternal allele. Genomic imprinting is highly prevalent in the brain, yet, until recently, its central roles in neural processes have not been fully appreciated. Here, we provide a comprehensive survey of adult and developmental brain functions influenced by imprinted genes, from neural development and wiring to synaptic function and plasticity, energy balance, social behaviors, emotions, and cognition. We further review the widespread identification of parental biases alongside monoallelic expression in brain tissues, discuss their potential roles in dosage regulation of key neural pathways, and suggest possible mechanisms underlying the dynamic regulation of imprinting in the brain. This review should help provide a better understanding of the significance of genomic imprinting in the normal and pathological brain of mammals including humans.

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“…Conversely, the proneuronal bHLH-protein neurogenin regulates the imprinted Dlk1-Gtl2 locus in the dorsal telencephalon [113] indicating bidirectional interactions between imprinted genes and proneuronal proteins. Genomic imprinting defects have been originally recognized for their role in early development of the embryo and placenta [9] and more recently for postnatal life [114] . New evidences suggest an additional role of variation in genomic imprinting in the mediation of environmental exposures, which is thought to associate with less severe consequences than those resulting from loss of genomic imprinting and might represent an important component of complex traits [115] .…”

Section: Resultsmentioning

confidence: 99%

ImprintedZac1in neural stem cells

Daniel

Schmidt-Edelkraut

Spengler

et al. 2015

WJSC

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Neural stem cells (NSCs) and imprinted genes play an important role in brain development. On historical grounds, these two determinants have been largely studied independently of each other. Recent evidence suggests, however, that NSCs can reset select genomic imprints to prevent precocious depletion of the stem cell reservoir. Moreover, imprinted genes like the transcriptional regulator Zac1 can fine tune neuronal vs astroglial differentiation of NSCs. Zac1 binds in a sequence-specific manner to pro-neuronal and imprinted genes to confer transcriptional regulation and furthermore coregulates members of the p53-family in NSCs. At the genome scale, Zac1 is a central hub of an imprinted gene network comprising genes with an important role for NSC quiescence, proliferation and differentiation. Overall, transcriptional, epigenomic, and genomic mechanisms seem to coordinate the functional relationships of NSCs and imprinted genes from development to maturation, and possibly aging.

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Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup

Abstract: A mouse genetic study reveals that a single gene acting in both mother and offspring has a central role in the uniquely mammalian phenomenon of nutrient provisioning through the placenta and the mammary gland.

Cited by 48 publications

References 48 publications

Tissue-specific regulation and function of Grb10 during growth and neuronal commitment

Tissue-specific regulation and function of Grb10 during growth and neuronal commitment

New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain

ImprintedZac1in neural stem cells

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