Motor neuron columnar fate imposed by sequential phases of Hox-c activity

Dasen, Jeremy S.; Liu, Jeh-Ping; Jessell, Thomas M.

doi:10.1038/nature02051

Cited by 344 publications

(429 citation statements)

References 49 publications

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“…Recent work on the developing vertebrate hindbrain and spinal cord have demonstrated a role for Hox genes in subdividing larger neuronal populations into neuronal subtypes (51)(52)(53)(54). Our present results show that four amphioxus Hox genes and two neuronal differentiation genes (amphioxus islet and AmphiERR) are expressed in nonoverlapping patterns in different epidermal sensory neurons.…”

Section: Discussionsupporting

confidence: 50%

Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

Schubert

Holland

Escrivà

et al. 2004

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

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In developing chordates, retinoic acid (RA) signaling patterns the rostrocaudal body axis globally and affects gene expression locally in some differentiating cell populations. Here we focus on development of epidermal sensory neurons in an invertebrate chordate (amphioxus) to determine how RA signaling influences their rostrocaudal distribution and gene expression (for AmphiCoe, a neural precursor gene; for amphioxus islet and AmphiERR, two neural differentiation genes; and for AmphiHox1, -3, -4, and -6). Treatments with RA or an RA antagonist (BMS009) shift the distribution of developing epidermal neurons anteriorly or posteriorly, respectively. These treatments also affect gene expression patterns in the epidermal neurons, suggesting that RA levels may influence specification of neuronal subtypes. Although colinear expression of Hox genes is well known for the amphioxus central nervous system, we find an unexpected comparable colinearity for AmphiHox1, -3, -4, and -6 in the developing epidermis; moreover, RA levels affect the anteroposterior extent of these Hox expression domains, suggesting that RA signaling controls a colinear Hox code for anteroposterior patterning of the amphioxus epidermis. Thus, in amphioxus, the developing peripheral nervous system appears to be structured by mechanisms parallel to those that structure the central nervous system. One can speculate that, during evolution, an ancestral deuterostome that structured its panepidermal nervous system with an RA-influenced Hox code gave rise to chordates in which this patterning mechanism persisted within the epidermal elements of the peripheral nervous system and was transferred to the neuroectoderm as the central nervous system condensed dorsally.

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Section: Discussionsupporting

confidence: 50%

Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

Schubert

Holland

Escrivà

et al. 2004

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

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“…The details of how this aspect of neuronal identity is controlled have only recently begun to emerge. Remarkably, some of the signals known to contribute to anterior-posterior patterning include those that function in dorsoventral patterning such as FGF and RA (Liu et al 2001), and the partitioning of groups of cells along the anterior-posterior axis appears to result from cross-repressive interactions between homeodomain proteins of the Hox family (Dasen et al 2003). Thus, similarities between the patterning of cells along these axes appear to exist, and insights into mechanisms regulating dorsoventral pattern provide a foundation for unravelling the details of anteriorposterior patterning.…”

Section: Discussionmentioning

confidence: 99%

“…It is clear, however, that further subdivisions of these five neuronal classes will emerge as more molecular markers are characterized and additional assays are employed to study their function. In part, this is likely to reflect the diversification of individual neuronal fates following their initial generation-this is already apparent for MNs where mechanisms that subdivide somatic MNs into pools of neurons that innervate different muscles are under intensive study (Liu et al 2001;Dasen et al 2003). In addition, mechanisms that increase the initial diversity of neuronal subtypes are also likely to operate.…”

Section: Gli Repressionmentioning

confidence: 99%

Regulatory pathways linking progenitor patterning, cell fates and neurogenesis in the ventral neural tube

Briscoe¹,

Novitch

2007

Phil. Trans. R. Soc. B

136

137

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The assembly of neural circuits in the vertebrate central nervous system depends on the organized generation of specific neuronal subtypes. Studies over recent years have begun to reveal the principles and elucidate some of the detailed mechanisms that underlie these processes. In general, exposure to different types and concentrations of signals directs neural progenitor populations to generate specific subtypes of neurons. These signals function by regulating the expression of intrinsic determinants, notably transcription factors, which specify the fate of cells as they differentiate into neurons. In this review, we illustrate these concepts by focusing on the generation of neurons in ventral regions of the spinal cord, where detailed knowledge of the mechanisms that regulate cell identity has provided insight into the development of a number of neuronal subtypes, including motor neurons. A greater knowledge of the molecular control of neural development is likely to have practical benefits in understanding the causes and consequences of neurological diseases. Moreover, recent studies have demonstrated how an understanding of normal neural development can be applied to direct differentiation of stem cells in vitro to specific neuronal subtypes. This type of rational manipulation of stem cells may represent the first step in the development of treatments based on therapeutic replacement of diseased or damaged nervous tissue.

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“…Interestingly, paralogous genes from different clusters have related AP expression domains but may respond to distinct dorsoventral patterning signals (Graham et al 1991;Davenne et al 1999). Recently, a functional relationship between Hox expression and MN specification was documented as HOXC6 and HOXC9 protein expression coincided with particular brachial and thoracic motoneurons (Dasen et al 2003). Ectopic expression of either protein induced both the extinction of the other and a concomitant change in MN subtype.…”

Section: Mammalian Genomes Contain 39mentioning

confidence: 99%

“…Ectopic expression of either protein induced both the extinction of the other and a concomitant change in MN subtype. Therefore, HOX cross-repressive interactions may establish distinct rostro-caudal MN fate as well as MN pool identity within a given columnar subtype (Dasen et al 2003). Likewise, Hoxd10 could specify the lateral motor column (LMC) at lumbar levels (Shah et al 2004).…”

Section: Mammalian Genomes Contain 39mentioning

confidence: 99%

HoxD cluster scanning deletions identify multiple defects leading to paralysis in the mouse mutant Ironside

Tarchini¹,

Huynh²,

Cox³

et al. 2005

Genes Dev.

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A spontaneous semidominant mutation (Ironside, Irn) was isolated in mice, leading to severe hindlimb paralysis following multiple deletions in cis at the HoxD locus. To understand its cellular and molecular etiology, we embarked on a comparative analysis using systematic HoxD cluster deletions, produced via targeted meiotic recombination (TAMERE). Different lines of mice were classified according to the severity of their paralyses, and subsequent analyses revealed that multiple causative factors were involved, alone or in combination, in the occurrence of this pathology. Among them are the loss of Hoxd10 function, the sum of remaining Hoxd gene activity, and the ectopic gain of function of the neighboring gene Evx2, all contributing to the mispositioning, the absence, or misidentification of specific lumbo-sacral pools of motoneurons, nerve root homeosis, and hindlimb innervation defects. These results highlight the importance of a systematic approach when studying such clustered gene families, and give insights into the function and regulation of Hox and Evx2 genes during early spinal cord development.[Keywords: Homeosis; peroneal nerve; chromosome engineering; motoneuron] Supplemental material is available at http://www.genesdev.org.

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Motor neuron columnar fate imposed by sequential phases of Hox-c activity

Cited by 344 publications

References 49 publications

Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

Regulatory pathways linking progenitor patterning, cell fates and neurogenesis in the ventral neural tube

HoxD cluster scanning deletions identify multiple defects leading to paralysis in the mouse mutant Ironside

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