SMAD4 is essential for generating subtypes of neurons during cerebellar development

Fernandes, Marie; Antoine, Michelle W.; Hébert, Jean M.

doi:10.1016/j.ydbio.2012.02.017

Cited by 27 publications

(40 citation statements)

References 42 publications

(65 reference statements)

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“…Together, our study and previous findings add to the understanding of the role of R-and Co-Smad in BMP signaling. In contrast to our findings, a previous report showed abnormal cerebellum development and severe ARL specification defects when Smad4 was inactivated using the same En1-Cre mouse line as ours but with a different Smad4 conditional allele (27). However, in another report using Nestin-Cre to delete Smad4 in the nervous system, there were only mild cerebellar phenotypes resembling those in our study (29).…”

Section: Discussioncontrasting

confidence: 99%

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Common Partner Smad-Independent Canonical Bone Morphogenetic Protein Signaling in the Specification Process of the Anterior Rhombic Lip during Cerebellum Development

Tong

Kwan

2013

Molecular and Cellular Biology

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Bone morphogenetic protein (BMP) signaling is critical for cerebellum development. However, the details of receptor regulatedSmad (R-Smad) and common partner Smad (Co-Smad, or Smad4) involvement are unclear. Here, we report that cerebellumspecific double conditional inactivation of Smad1 and Smad5 (Smad1/5) results in cerebellar hypoplasia, reduced granule cell numbers, and disorganized Purkinje neuron migration during embryonic development. However, single conditional inactivation of either Smad1 or Smad5 did not result in cerebellar abnormalities. Surprisingly, conditional inactivation of Smad4, which is considered to be the central mediator of canonical BMP-Smad signaling, resulted only in very mild cerebellar defects. Conditional inactivation of Smad1/5 led to developmental defects in the anterior rhombic lip (ARL), as shown by reduced cell proliferation and loss of Pax6 and Atoh1 expression. These defects subsequently caused the loss of the nuclear transitory zone and a region of the deep cerebellar nuclei. The normal maturation of the remaining granule cell precursors in the external granular layer (EGL) suggests Smad1/5 signaling is required for the specification process in ARL but not for the subsequent EGL development. Our results demonstrate functional redundancy for Smad1 and Smad5 but functional discrepancy between Smad1/5 and Smad4 during cerebellum development.

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Section: Discussioncontrasting

confidence: 99%

“…Activated Smad1, -5, and -8 form complexes with common partner Smad (Co-Smad, or Smad4) and translocate into the nucleus, where they regulate the transcription of target genes (23)(24)(25). Both R-Smads and Co-Smad are expressed in the embryonic cerebellum (27). Bmpr1a and Bmpr1b encode the type I receptors for BMP signaling.…”

mentioning

confidence: 99%

Common Partner Smad-Independent Canonical Bone Morphogenetic Protein Signaling in the Specification Process of the Anterior Rhombic Lip during Cerebellum Development

Tong

Kwan

2013

Molecular and Cellular Biology

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“…BMP signalling result in cerebellar defects (Fernandes et al, 2012;Tong and Kwan, 2013), although the interpretation of such experiments is confounded by earlier roles for BMP signalling during dorsal neural tube patterning (Alder et al, 1999;Lee and Jessell, 1999;Broom et al, 2012).…”

Section: Balancing Proliferation and Differentiation In The External mentioning

confidence: 99%

“…roof plate (Alder et al, 1999;Fernandes et al, 2012;Tong and Kwan, 2013). Although this might suggest that the rhombic lip is a dorsally allocated progenitor pool, it is perhaps more appropriate to consider it as a zone of dynamic induction at the edge of the ventricular zone.…”

Section: Blurred Lines: Gabaergic and Glutamatergic Progenitor Domainmentioning

confidence: 99%

Development of the cerebellum: simple steps to make a ‘little brain’

Green²,

2014

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The cerebellum is a pre-eminent model for the study of neurogenesis and circuit assembly. Increasing interest in the cerebellum as a participant in higher cognitive processes and as a locus for a range of disorders and diseases make this simple yet elusive structure an important model in a number of fields. In recent years, our understanding of some of the more familiar aspects of cerebellar growth, such as its territorial allocation and the origin of its various cell types, has undergone major recalibration. Furthermore, owing to its stereotyped circuitry across a range of species, insights from a variety of species have contributed to an increasingly rich picture of how this system develops. Here, we review these recent advances and explore three distinct aspects of cerebellar development -allocation of the cerebellar anlage, the significance of transit amplification and the generation of neuronal diversity -each defined by distinct regulatory mechanisms and each with special significance for health and disease.

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“…BMPs are also involved in regulation of a transcriptional network to generate forebrain cholinergic neurons (Bissonnette et al, 2011). They also determine a temporally and spatially restricted requirement for generation of glutamatergic neurons in cerebellum (Fernandes et al, 2012). …”

Section: Bmps In Nervous System Development and Maintenancementioning

confidence: 99%

BMP signaling in telencephalic neural cell specification and maturation

Gámez¹,

Rodríguez-Carballo²,

Ventura³

2013

Front. Cell. Neurosci.

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Bone morphogenetic proteins (BMPs) make up a family of morphogens that are critical for patterning, development, and function of the central and peripheral nervous system. Their effects on neural cells are pleiotropic and highly dynamic depending on the stage of development and the local niche. Neural cells display a broad expression profile of BMP ligands, receptors, and transducer molecules. Moreover, interactions of BMP signaling with other incoming morphogens and signaling pathways are crucial for most of these processes. The key role of BMP signaling suggests that it includes many regulatory mechanisms that restrict BMP activity both temporally and spatially. BMPs affect neural cell fate specification in a dynamic fashion. Initially they inhibit proliferation of neural precursors and promote the first steps in neuronal differentiation. Later on, BMP signaling effects switch from neuronal induction to promotion of astroglial identity and inhibition of neuronal or oligodendroglial lineage commitment. Furthermore, in postmitotic cells, BMPs regulate cell survival and death, to modulate neuronal subtype specification, promote dendritic and axonal growth and induce synapse formation and stabilization. In this review, we examine the canonical and non-canonical mechanisms of BMP signal transduction. Moreover, we focus on the specific role of BMPs in the nervous system including their ability to regulate neural stem cell proliferation, self-renewal, lineage specification, and neuronal function.

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SMAD4 is essential for generating subtypes of neurons during cerebellar development

Cited by 27 publications

References 42 publications

Common Partner Smad-Independent Canonical Bone Morphogenetic Protein Signaling in the Specification Process of the Anterior Rhombic Lip during Cerebellum Development

Common Partner Smad-Independent Canonical Bone Morphogenetic Protein Signaling in the Specification Process of the Anterior Rhombic Lip during Cerebellum Development

Development of the cerebellum: simple steps to make a ‘little brain’

BMP signaling in telencephalic neural cell specification and maturation

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