Two Critical Periods of Sonic Hedgehog Signaling Required for the Specification of Motor Neuron Identity

Ericson, Johan; Morton, Susan; Kawakami, Atsushi; Roelink, Henk; Jessell, Thomas M.

doi:10.1016/s0092-8674(00)81386-0

Cited by 810 publications

(633 citation statements)

References 52 publications

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“…Similarly, Shh signaling is not required for the survival of DA SNpc in a cell‐autonomous manner after E16 in mice (Zhou et al, 2016), but it is required at this late developmental time for functional specification of DA SNpc (Zhou et al, 2016). Interestingly, Shh has a distinct role over other cholinergic neurons, as an enhancer of postmitotic survival of basal forebrain cholinergic neurons (Reilly, Karavanova, Williams, Mahanthappa, & Allendoerfer, 2002) and as differentiation factor for motor neurons (Ericson, Morton, Kawakami, Roelink, & Jessell, 1996). …”

Section: Discussionmentioning

confidence: 99%

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Sanchez-Garcia

Nieto-González

García-Junco-Clemente

et al. 2018

Aging Cell

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The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.

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Section: Discussionmentioning

confidence: 99%

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Sanchez-Garcia

Nieto-González

García-Junco-Clemente

et al. 2018

Aging Cell

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“…In chick explant studies, sonic hedgehog (shh) -expressing tissue such as the notochord or recombinant Shh protein are sufficient to induce motor neurons in ventral neural tube explants derived from various axial levels, and this effect is blocked by antiShh antibodies Tanabe et al, 1995;Ericson et al, 1996). Furthermore, motor neurons are completely absent in Shh knockout mouse embryos (Chiang et al, 1996;Litingtung and Chiang, 2000a).…”

Section: Induction Of Branchiomotor Neuronsmentioning

confidence: 99%

Turning heads: Development of vertebrate branchiomotor neurons

Chandrasekhar

2003

Developmental Dynamics

164

204

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The cranial motor neurons innervate muscles that control eye, jaw, and facial movements of the vertebrate head and parasympathetic neurons that innervate certain glands and organs. These efferent neurons develop at characteristic locations in the brainstem, and their axons exit the neural tube in well-defined trajectories to innervate target tissues. This review is focused on a subset of cranial motor neurons called the branchiomotor neurons, which innervate muscles derived from the branchial (pharyngeal) arches. First, the organization of the branchiomotor pathways in zebrafish, chick, and mouse embryos will be compared, and the underlying axon guidance mechanisms will be addressed. Next, the molecular mechanisms that generate branchiomotor neurons and specify their identities will be discussed. Finally, the caudally directed or tangential migration of facial branchiomotor neurons will be examined. Given the advances in the characterization and analysis of vertebrate genomes, we can expect rapid progress in elucidating the cellular and molecular mechanisms underlying the development of these vital neuronal networks.

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“…In particular, Shh signalling plays a key role in neural development. In the developing vertebrate, Shh is expressed ventral to the neural tube and a gradient of signalling from ventral to dorsal is responsible for the patterning and specification of five ventral neural progenitor sub-types in a manner inversely proportional to the distance from this source [20]. The neural progenitor sub-types then differentiate into distinct neuronal subtypes, including commissural neurons, association neurons, motor neurons, and ventral interneurons [21].…”

Section: Introductionmentioning

confidence: 99%

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

et al. 2015

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Induced pluripotent stem cells (iPSCs) are generated from adult somatic cells through the induction of key transcription factors that restore the ability to become any cell type found in the body. These cells are of interest for tissue engineering due to their potential for developing patient-specific therapies. As the technology for generating iPSCs advances, it is important to concurrently investigate protocols for the efficient differentiation of these cells to desired downstream phenotypes in combination with biomaterial scaffolds as a way of engineering neural tissue. For such applications, the generation of neurons within three dimensional fibrin scaffolds has been well characterized as a cell-delivery platform for murine embryonic stem cells (ESCs) but has not yet been applied to murine iPSCs. Given that iPSCs have been reported to differentiate less effectively than ESCs, a key objective of this investigation is to maximize the proportion of iPSC-derived neurons in fibrin through the choice of differentiation protocol. To this end, this study compares two EB-mediated protocols for generating neurons from murine iPSCs and ESCs: an 8-day 4-/4+ protocol using soluble retinoic acid in the last 4 days and a 6-day 2-/4+ protocol using soluble retinoic acid and the small molecule sonic hedgehog agonist purmorphamine in the last 4 days. EBs were then seeded in fibrin scaffolds for 14 days to allow further differentiation into neurons. EBs generated by the 2-/4+ protocol yielded a higher percentage of neurons compared to those from the 4-/4+ protocol for both iPSCs and ESCs. The results demonstrate the successful translation of the fibrin-based cell-delivery platform for use with murine iPSCs and furthermore that the proportion of neurons generated from murine iPSC-derived EBs seeded in fibrin can be maximized using the 2-/4+ differentiation protocol. Together, these findings validate the further exploration of 3D fibrin-based scaffolds as a method of delivering neuronal cells derived from iPSCs -an important step toward the development of iPSC-based tissue engineering strategies for spinal cord injury repair.

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Two Critical Periods of Sonic Hedgehog Signaling Required for the Specification of Motor Neuron Identity

Cited by 810 publications

References 52 publications

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Turning heads: Development of vertebrate branchiomotor neurons

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

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