Expression and regulation of the retinoic acid synthetic enzyme RALDH‐2 in the embryonic chicken wing

Berggren, Kirsten; Ezerman, Elizabeth B.; McCaffery, Peter; Forehand, Cynthia J.

doi:10.1002/dvdy.1166

Cited by 30 publications

(29 citation statements)

References 64 publications

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“…RA synthesis by RALDH2 from mesenchyme or mesenchymal derivatives guides development in several embryonic tissues. RA sources include the anterior somites, which are derived from paraxial mesenchyme and provide RA for the early posterior rhombomeres, mesenchyme in the developing mouse inner ear (Romand et al, 2001), and limb mesenchyme where RA may be involved in cartilage development and skeletal muscle differentiation (Berggren et al, 2001). However, few studies have hitherto investigated the influence of the meninges on the developing brain.…”

Section: Discussionmentioning

confidence: 99%

The Meninges Is a Source of Retinoic Acid for the Late-Developing Hindbrain

et al. 2003

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One general function for retinoic acid (RA) is pattern organization in the CNS. This regulatory factor has an essential role in spinal cord motor neuron and early posterior hindbrain development. In the anterior CNS, however, there is only a limited number of foci of RA synthesis, and less attention has been placed on regions such as the anterior hindbrain where RA synthesizing enzymes are absent. This study shows that a rich source of RA lies around the hindbrain from the RA synthetic enzyme retinaldehyde dehydrogenase-2 (RALDH2) present in the surrounding meninges and mesenchyme by embryonic day 13. RALDH2 is not distributed uniformly throughout the meninges but is restricted to territories over the developing hindbrain, suggesting that RA signaling may be localized to those regions. Further regulation of RA signaling is provided by the presence of a RA sink in the form of the CYP26B1 RA catabolic enzyme expressed in deeper regions of the brain. As a guide to the neural anatomy of hindbrain RA signaling, we used a mouse transgenic for a lacZ reporter gene driven by a RA response element (RAREhsplacZ) to identify regions of RA signaling. This reporter mouse provides evidence that RA signaling in the hindbrain after embryonic day 13 occurs in the regions of the cerebellum and precerebellar system adjacent to sources of RA, including the inferior olive and the pontine nuclei.

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Section: Discussionmentioning

confidence: 99%

The Meninges Is a Source of Retinoic Acid for the Late-Developing Hindbrain

et al. 2003

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“…Furthermore, sites of RALDH2 expression correlate well with the presence of endogenous retinoids and the localization of cells that respond to RA; chondrocytes and osteoblast progenitors. It is noteworthy that in embryonic chick limb mesoderm there is little RALDH2, it is absent in cartilage although it is highly expressed in the perichondrium, as it is in antler (Berggren et al 2001). In the antler, as in the developing limb, chondrocytes are an important RA target; in vitro RA treatment leads to loss of the differentiated chondrocyte phenotype.…”

Section: Local Factors That Regulate Antler Regenerationmentioning

confidence: 99%

Exploring the mechanisms regulating regeneration of deer antlers

Price

Allen

2004

Phil. Trans. R. Soc. Lond. B

110

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Deer antlers are the only mammalian appendages capable of repeated rounds of regeneration; every year they are shed and regrow from a blastema into large branched structures of cartilage and bone that are used for fighting and display. Longitudinal growth is by a process of modified endochondral ossification and in some species this can exceed 2 cm per day, representing the fastest rate of organ growth in the animal kingdom. However, despite their value as a unique model of mammalian regeneration the underlying mechanisms remain poorly understood. We review what is currently known about the local and systemic regulation of antler regeneration and some of the many unsolved questions of antler physiology are discussed. Molecules that we have identified as having potentially important local roles in antlers include parathyroid hormone-related peptide and retinoic acid (RA). Both are present in the blastema and in the rapidly growing antler where they regulate the differentiation of chondrocytes, osteoblasts and osteoclasts in vitro. Recent studies have shown that blockade of RA signalling can alter cellular differentiation in the blastema in vivo. The trigger that regulates the expression of these local signals is likely to be changing levels of sex steroids because the process of antler regeneration is linked to the reproductive cycle. The natural assumption has been that the most important hormone is testosterone, however, at a cellular level oestrogen may be a more significant regulator. Our data suggest that exogenous oestrogen acts as a 'brake', inhibiting the proliferation of progenitor cells in the antler tip while stimulating their differentiation, thus inhibiting continued growth. Deciphering the mechanism(s) by which sex steroids regulate cell-cycle progression and cellular differentiation in antlers may help to address why regeneration is limited in other mammalian tissues.

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“…Interestingly, retinaldehyde dehydrogenase type 2 (RALDH2), a major retinoic acid (RA) synthesizing enzyme, is first expressed (or re-expressed) in limb mesenchyme around St. 23 (wing; Berggren et al, 1999Berggren et al, , 2001 or St. 24 (hindlimb;Wang and Scott, 2005).…”

Section: Onset Of Ets Expression Is Not Accelerated By An Early Ectopmentioning

confidence: 99%

“…Retinoid signaling from limb mesenchyme begins about the time that axons enter the limb (Berggren et al, 1999(Berggren et al, , 2001Wang and Scott, 2005) and motor neurons begin to express Er81, suggesting that it could play a role in initiating Er81 expression, either directly or indirectly. Whereas increasing RA levels in the limb at earlier stages induced axons to enter the limb precociously, it did not alter either the spatial or temporal pattern of ETS initiation.…”

Section: Mesenchymal Signals Can Initiate Ets Expressionmentioning

confidence: 99%