An Essential Requirement for Fgf10 in Pinna Extension Sheds Light on Auricle Defects in LADD Syndrome.
An Essential Requirement for Fgf10 in Pinna Extension Sheds Light on Auricle Defects in LADD Syndrome.
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DOI：
10.3389/fcell.2020.609643
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发表时间：
2020
影响因子：
5.5
通讯作者：
Tucker AS
中科院分区：
文献类型：
--
作者：
Zhang Y;Fons JM;Hajihosseini MK;Zhang T;Tucker AS
耳廓(或耳廓)是外耳的一部分，起到捕捉声音并将声音输送到中耳的作用。在许多颅面综合征中，耳廓是缺陷的，包括由FGF10或其受体FGFR2b突变引起的舌耳-齿-指(LAD)综合征。在这里，我们研究了Fgf10基因敲除小鼠的耳廓缺陷。我们发现，Fgf10在发育中的外耳的肌肉和软骨中都有表达，信号的丢失导致耳廓在耳道上的正常延伸失败。Fgf10在神经嵴中的条件性敲除不能概括这种表型，提示这种缺陷是由于肌肉中Fgf10的丢失，或者Fgf10的这种来源可以弥补形成软骨的丢失。Fgf10基因缺失小鼠的缺陷是由增殖减少而不是细胞死亡增加驱动的，这可以通过抑制外植体培养中的细胞增殖来部分表现出来。总体而言，我们强调了可能导致LAD综合征患者观察到的表型的机制，并潜在地解释了在其他综合征中观察到的类似的低置和杯状耳朵的形成。
The pinna (or auricle) is part of the external ear, acting to capture and funnel sound toward the middle ear. The pinna is defective in a number of craniofacial syndromes, including Lacrimo-auriculo-dento-digital (LADD) syndrome, which is caused by mutations in FGF10 or its receptor FGFR2b. Here we study pinna defects in the Fgf10 knockout mouse. We show that Fgf10 is expressed in both the muscles and forming cartilage of the developing external ear, with loss of signaling leading to a failure in the normal extension of the pinna over the ear canal. Conditional knockout of Fgf10 in the neural crest fails to recapitulate this phenotype, suggesting that the defect is due to loss of Fgf10 from the muscles, or that this source of Fgf10 can compensate for loss in the forming cartilage. The defect in the Fgf10 null mouse is driven by a reduction in proliferation, rather than an increase in cell death, which can be partially phenocopied by inhibiting cell proliferation in explant culture. Overall, we highlight the mechanisms that could lead to the phenotype observed in LADD syndrome patients and potentially explain the formation of similar low-set and cup shaped ears observed in other syndromes.
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DOI：
10.1242/dev.194654
发表时间：
2020-12-14
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Fons JM;Mozaffari M;Malik D;Marshall AR;Connor S;Greene NDE;Tucker AS
通讯作者：
Tucker AS
影响因子：
3.5
作者：
Kelly, RG;Jerome-Majewska, LA;Papaioannou, VE
通讯作者：
Papaioannou, VE
影响因子：
0.9
作者：
Cabrejo, Raysa;Persing, John;Alperovich, Michael
通讯作者：
Alperovich, Michael
影响因子：
2.7
作者：
KING, JA;MARKER, PC;KINGSLEY, DM
通讯作者：
KINGSLEY, DM
在胚胎发育过程中，新型成纤维细胞生长因子10（FGF10）敲入小鼠系的表征。
影响因子：
3.7
作者：
El Agha E;Al Alam D;Carraro G;MacKenzie B;Goth K;De Langhe SP;Voswinckel R;Hajihosseini MK;Rehan VK;Bellusci S
通讯作者：
Bellusci S