Developmental Programming of Branching Morphogenesis in the Kidney.
The kidney developmental program encodes the intricate branching and organization of approximately 1 million functional units (nephrons). Branching regulation is poorly understood, as is the source of a 10-fold variation in nephron number. Notably, low nephron count increases the risk for developing...
| Published in: | Journal of the American Society of Nephrology (JASN) Vol. 26; no. 10; pp. 2414 - 2423 |
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| Main Authors: | , , |
| Format: | research Journal Article |
| Published: |
Lippincott Williams & Wilkins
Oct2015
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=141596404&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 141596404 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10466673 1X25 jtl: Journal of the American Society of Nephrology (JASN) issn: 10466673 maglogo: N pubinfo: dt: Oct2015 vid: 26 iid: 10 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 141596404 141596404 NLM25644110 141596404 10.1681/ASN.2014090886 NLM25644110 141596404 ppf: 2414 ppct: 9 formats: tig: atl: Developmental Programming of Branching Morphogenesis in the Kidney. aug: au: Sampogna, Rosemary V Schneider, Laura Al-Awqati, Qais affil: Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York sug: subj: Kidney Embryology Fetal Development Physiology Nephrons Embryology Mice Animal Studies Validation Studies Comparative Studies Evaluation Research Multicenter Studies Clinical Assessment Tools ab: The kidney developmental program encodes the intricate branching and organization of approximately 1 million functional units (nephrons). Branching regulation is poorly understood, as is the source of a 10-fold variation in nephron number. Notably, low nephron count increases the risk for developing hypertension and renal failure. To better understand the source of this variation, we analyzed the complete gestational trajectory of mouse kidney development. We constructed a computerized architectural map of the branching process throughout fetal life and found that organogenesis is composed of two distinct developmental phases, each with stage-specific rate and morphologic parameters. The early phase is characterized by a rapid acceleration in branching rate and by branching divisions that repeat with relatively reproducible morphology. The latter phase, however, is notable for a significantly decreased yet constant branching rate and the presence of nonstereotyped branching events that generate progressive variability in tree morphology until birth. Our map identifies and quantitates the contribution of four developmental mechanisms that guide organogenesis: growth, patterning, branching rate, and nephron induction. When applied to organs that developed under conditions of malnutrition or in the setting of growth factor mutation, our normative map provided an essential link between kidney architecture and the fundamental morphogenetic mechanisms that guide development. This morphogenetic map is expected to find widespread applications and help identify modifiable targets to prevent developmental programming of common diseases. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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