Teashirt 3 Regulates Development of Neurons Involved in Both Respiratory Rhythm and Airflow Control

Caubit, Xavier; Thoby‐Brisson, Muriel; Voituron, Nicolas; Filippi, P; Bévengut, Michelle; Faralli, Hervé; Zanella, Sébastien; Fortin, Gilles; Hilaire, Gérard; Fasano, Laurent

doi:10.1523/jneurosci.1765-10.2010

Cited by 47 publications

(53 citation statements)

References 44 publications

(79 reference statements)

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“…3A-C). As in other mutants with impaired RTN function Rose et al, 2009;Caubit et al, 2010), pre-BötC oscillator activity in transverse medullary slices was not affected (Fig. 3D-F ).…”

Section: Egr2supporting

confidence: 72%

Breathing without CO₂Chemosensitivity in ConditionalPhox2bMutants

Ramanantsoa¹,

Hirsch²,

et al. 2011

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Breathing is a spontaneous, rhythmic motor behavior critical for maintaining O 2 , CO 2 , and pH homeostasis. In mammals, it is generated by a neuronal network in the lower brainstem, the respiratory rhythm generator (Feldman et al., 2003). A century-old tenet in respiratory physiology posits that the respiratory chemoreflex, the stimulation of breathing by an increase in partial pressure of CO 2 in the blood, is indispensable for rhythmic breathing. Here we have revisited this postulate with the help of mouse genetics. We have engineered a conditional mouse mutant in which the toxic PHOX2B 27Ala mutation that causes congenital central hypoventilation syndrome in man is targeted to the retrotrapezoid nucleus, a site essential for central chemosensitivity. The mutants lack a retrotrapezoid nucleus and their breathing is not stimulated by elevated CO 2 at least up to postnatal day 9 and they barely respond as juveniles, but nevertheless survive, breathe normally beyond the first days after birth, and maintain blood PCO 2 within the normal range. Input from peripheral chemoreceptors that sense PO 2 in the blood appears to compensate for the missing CO 2 response since silencing them by high O 2 abolishes rhythmic breathing. CO 2 chemosensitivity partially recovered in adulthood. Hence, during the early life of rodents, the excitatory input normally afforded by elevated CO 2 is dispensable for life-sustaining breathing and maintaining CO 2 homeostasis in the blood.

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“…3A-C). As in other mutants with impaired RTN function Rose et al, 2009;Caubit et al, 2010), pre-BötC oscillator activity in transverse medullary slices was not affected (Fig. 3D-F ).…”

Section: Egr2supporting

confidence: 72%

Breathing without CO₂Chemosensitivity in ConditionalPhox2bMutants

Ramanantsoa¹,

Hirsch²,

et al. 2011

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“…This pathway consists of two networks that control involuntary respiration (31). The first is the central neural respiratory network located in the brainstem, which includes cranial motor neurons of the nucleus ambiguus (NA).…”

Section: Loss Ofmentioning

confidence: 99%

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease

Nguyen¹,

Weaver

et al. 2014

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

187

196

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Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease. Motor neuron diseases (MNDs), including ALS and spastic paraplegia (SP), are characterized by the progressive, lengthdependent degeneration of motor neurons, leading to muscle atrophy, paralysis, and, in some cases, premature death. There are both inherited and sporadic forms of MNDs, which can affect upper motor neurons, lower motor neurons, or both. Although the molecular and cellular causes of most MNDs are unknown, many are associated with defects in axonal transport of cellular components required for neuron function and maintenance (1-6).A subset of MNDs is associated with impaired mitochondrial respiration and mitochondrial distribution. This observation has led to the hypothesis that neurodegeneration results from defects in mitochondrial motility and distribution, which, in turn, cause subcellular ATP depletion and interfere with mitochondrial calcium ([Ca 2+ ] m ) buffering at sites of high synaptic activity (reviewed in ref. 7). It is not known, however, whether mitochondrial motility defects are a primary cause or a secondary consequence of MND progression. In addition, it has been difficult to isolate the primary effect of mitochondrial motility defects in MNDs because most mutations that impair mitochondrial motility in neurons also affect transport of other organelles and vesicles (1,(8)(9)(10)(11).In mammals, the movement of neuronal mitochondria between the cell body and the synapse is controlled by adaptors called trafficking kinesin proteins (Trak1 and Trak2) and molecular motors (kinesin heavy chain and dynein), which transport the organelle in the anterograde or retrograde direction along axonal microtubule tracks (7,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Mitochondrial Rho (Miro) GTPase proteins are critical for transport because they are the only known surface receptors that attach mitochondria to...

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“…In both flies and frogs, Teashirt can localize to the nucleus and bind β-catenin, but its exact molecular function remains unclear Onai et al, 2007). In other vertebrates, Teashirt proteins have been implicated in myogenesis and in the development of the nervous system, particularly the specification of hindbrain structures; whether Teashirt functions with the Wnt pathway is unknown in several of these contexts (Koebernick et al, 2006;Caubit et al, 2010;Erickson et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

teashirt is required for head-versus-tail regeneration polarity in planarians

et al. 2015

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Regeneration requires that the identities of new cells are properly specified to replace missing tissues. The Wnt signaling pathway serves a central role in specifying posterior cell fates during planarian regeneration. We identified a gene encoding a homolog of the Teashirt family of zinc-finger proteins in the planarian Schmidtea mediterranea to be a target of Wnt signaling in intact animals and at posterior-facing wounds. Inhibition of Smed-teashirt (teashirt) by RNA interference (RNAi) resulted in the regeneration of heads in place of tails, a phenotype previously observed with RNAi of the Wnt pathway genes β-catenin-1, wnt1, Dvl-1/2 or wntless. teashirt was required for β-catenin-1-dependent activation of posterior genes during regeneration. These findings identify teashirt as a transcriptional target of Wnt signaling required for Wnt-mediated specification of posterior blastemas.

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Teashirt 3 Regulates Development of Neurons Involved in Both Respiratory Rhythm and Airflow Control

Cited by 47 publications

References 44 publications

Breathing without CO₂Chemosensitivity in ConditionalPhox2bMutants

Breathing without CO₂Chemosensitivity in ConditionalPhox2bMutants

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease

teashirt is required for head-versus-tail regeneration polarity in planarians

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Teashirt 3 Regulates Development of Neurons Involved in Both Respiratory Rhythm and Airflow Control

Cited by 47 publications

References 44 publications

Breathing without CO2Chemosensitivity in ConditionalPhox2bMutants

Breathing without CO2Chemosensitivity in ConditionalPhox2bMutants

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease

teashirt is required for head-versus-tail regeneration polarity in planarians

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Breathing without CO₂Chemosensitivity in ConditionalPhox2bMutants

Breathing without CO₂Chemosensitivity in ConditionalPhox2bMutants