The Role of Retinoic Acid in Establishing the Early Limb Bud

Feneck, Eleanor M.; Logan, Malcolm

doi:10.3390/biom10020312

Cited by 10 publications

(7 citation statements)

References 43 publications

(57 reference statements)

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“…Thus, during cardiopulmonary development, Tbx5 regulates production of three key paracrine signals, RA and Wnt directly via Tbx5-dependent enhancers and Hh indirectly via a RA-dependent enhancer. These interdependent signaling loops ensure that the lung primordia and pSHF-derived atria and pulmonary vessels from adjacent to one another, in preparation for the coordinated morphogenesis and functional integration of these two organ systems during development.T-box TFs and RA: a conserved regulatory node disrupted in cardiopulmonary and limb birth defectsIntegrated regulatory loops between Tbx5, RA, and FGF regulate limb development and lung branching morphogenesis in addition to SHF cardiac development(Nishimoto et al 2015;Arora et al 2012;Feneck and Logan 2020). We show that Tbx5 and RA form a positive feedforward loop in the pSHF; in this domain Tbx5 directly maintains Aldh1a2-dependent RA production while RA maintains tbx5 expression.…”

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confidence: 78%

“…Integrated regulatory loops between Tbx5, RA, and FGF regulate limb development and lung branching morphogenesis in addition to SHF cardiac development ( Nishimoto et al, 2015 ; Arora et al, 2012 ; Feneck and Logan, 2020 ). We show that Tbx5 and RA form a positive feedforward loop in the pSHF; in this domain, Tbx5 directly maintains Aldh1a2-dependent RA production while RA maintains tbx5 expression.…”

Section: Discussionmentioning

confidence: 99%

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Tbx5 drives Aldh1a2 expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development

Rankin

Steimle

Yang

et al. 2021

eLife

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The gene regulatory networks that coordinate the development of the cardiac and pulmonary systems are essential for terrestrial life but poorly understood. The T-box transcription factor Tbx5 is critical for both pulmonary specification and heart development, but how these activities are mechanistically integrated remains unclear. Here using Xenopus and mouse embryos, we establish molecular links between Tbx5 and retinoic acid (RA)-signaling in the mesoderm and between RA signaling and sonic hedgehog expression in the endoderm to unveil a conserved RA-Hedgehog-Wnt signaling cascade coordinating cardiopulmonary development. We demonstrate that Tbx5 directly maintains expression of aldh1a2, the RA-synthesizing enzyme, in the foregut lateral plate mesoderm via an evolutionarily conserved intronic enhancer. Tbx5 promotes posterior second heart field identity in a positive feedback loop with RA, antagonizing a Fgf8-Cyp regulatory module to restrict FGF activity to the anterior. We find that Tbx5/Aldh1a2-dependent RA signaling directly activates shh transcription in the adjacent foregut endoderm through a conserved MACS1 enhancer. Hedgehog signaling coordinates with Tbx5 in the mesoderm to activate expression of wnt2/2b, which induces pulmonary fate in the foregut endoderm. These results provide mechanistic insight into the interrelationship between heart and lung development informing cardiopulmonary evolution and birth defects.

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mentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Tbx5 drives Aldh1a2 expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development

Rankin

Steimle

Yang

et al. 2021

eLife

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“…Recent evidence suggests that this transition from proximal signalling to autonomous timing occurs during forearm/zeugopod specification (2,6,8) . Retinoic acid emanating from the trunk of the embryo is considered to be involved in forelimb initiation, and is also implicated as the extrinsic signal involved in proximal specification (4,5,(9)(10)(11) . Accordingly, specification of positional values that encode the different segments of the limb is associated with the progressive expression of genes encoding 5' Hox proteins: Hoxa/d10 provides a read-out of stylopod specification, and then Hoxa/d11 followed by Hoxa/d13 provide read-outs of zeugopod and autopod specification, respectively (12,13) .…”

Section: Introductionmentioning

confidence: 99%

Species-specific developmental timing dictates expansion of the avian wing skeletal pattern

Stainton¹,

Towers²

2021

Preprint

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How development is timed between differently sized species is a fundamental question in biology. To address this problem, we compared wing development in the quail and the larger chick. We reveal that developmental timing is faster in the quail than in the chick, and is associated with pattern specification, proliferation, organiser duration, differentiation and apoptosis. However, developmental timing is independent of the growth rate, which is equivalent between both species, and therefore scales pattern to the size of the wing. We reveal that developmental timing can be either maintained or reset in interspecies tissue grafts, and we implicate retinoic acid as the resetting signal. Accordingly, retinoic acid can switch species developmental timing and rescale pattern, both between the quail and chick, and the chick and the larger turkey. We suggest that the scaling of pattern to wing bud size is achieved by the modulation of developmental timing against a comparable rate of growth.

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“…It is well documented that vitamin A is essential for human survival at every stage of life. It has critical functions during embryogenesis, the development of organs, reproduction, immunity, and vision ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ). Besides these important roles, new physiological functions of vitamin A are continuously being discovered in the fields of neuroscience and lipid research ( 9 , 10 ).…”

mentioning

confidence: 99%

Retinoids in the visual cycle: role of the retinal G protein-coupled receptor

Choi

Daruwalla

Suh

et al. 2021

Journal of Lipid Research

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Driven by the energy of a photon, the visual pigments in rod and cone photoreceptor cells isomerize 11-cis-retinal to the all-trans configuration. This photochemical reaction initiates the signal transduction pathway that eventually leads to the transmission of a visual signal to the brain and leaves the opsins insensitive to further light stimulation. For the eye to restore light sensitivity, opsins require recharging with 11-cis-retinal. This trans–cis back conversion is achieved through a series of enzymatic reactions composing the retinoid (visual) cycle. Although it is evident that the classical retinoid cycle is critical for vision, the existence of an adjunct pathway for 11-cis-retinal regeneration has been debated for many years. Retinal pigment epithelium (RPE)–retinal G protein-coupled receptor (RGR) has been identified previously as a mammalian retinaldehyde photoisomerase homologous to retinochrome found in invertebrates. Using pharmacological, genetic, and biochemical approaches, researchers have now established the physiological relevance of the RGR in 11-cis-retinal regeneration. The photoisomerase activity of RGR in the RPE and Müller glia explains how the eye can remain responsive in daylight. In this review, we will focus on retinoid metabolism in the eye and visual chromophore regeneration mediated by RGR.

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The Role of Retinoic Acid in Establishing the Early Limb Bud

Cited by 10 publications

References 43 publications

Tbx5 drives Aldh1a2 expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development

Tbx5 drives Aldh1a2 expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development

Species-specific developmental timing dictates expansion of the avian wing skeletal pattern

Retinoids in the visual cycle: role of the retinal G protein-coupled receptor

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