Sara Ahlgren, PhD Assistant Professor Pediatrics, CMRC Craniofacial growth and development Curricula: Developmental Biology Molecular Biology and Genetics E-mail:   s-ahlgren@northwestern.edu

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My lab studies the process of craniofacial growth, and the role different genes play in coordinating growth and patterning of the head. These studies focus on both normal development and the abnormal development produced by teratogens, which are chemicals which, by definition, result in birth defects. One of the most common teratogens is ethanol, which causes a stereotypic set of brain and facial abnormalities when ingested during early pregnancy. Research in my lab has established that one target of ethanol is the hedgehog signaling pathway, which is greatly reduced in chick embryos exposed to ethanol early in development.

One vertebrate hedgehog gene, Sonic hedgehog, appears to play a pivotal role in normal craniofacial development. This is evidenced by the finding that a reduction in this gene has profound effects on the cranial neural crest, a population of cells which originate in the neural tube then migrate to form the cranial ganglia and the cranial skeleton. Loss of these cells leads to both size and pattern disruptions. Human patients with loss of one copy of SHH have a birth defect known as holoprosencephaly, which is a failure of the forebrain to split into two halves. Patients with holoprosencephaly typically have craniofacial features as well, suggesting a link between brain and face development.

The first set of ongoing research projects in my lab expand the understanding of how ethanol affects developing embryos, using two different model systems. The better established model of fetal alcohol syndrome is the chick embryo. The research using this model system will concentrate on the timing of the effects of ethanol and using array technology to find other genes which are altered after exposure to ethanol. In addition, we plan to expand the studies to examine the effects of ethanol on brain development. The second model system for fetal alcohol studies is the zebrafish. Although it has not been used as a true model for fetal alcohol effects, the zebrafish has been used as a classical teratology model system for high dose effects of ethanol (and many other lab chemicals). The current experiments in the lab are establishing that there are effects of ethanol at clinically relevant doses. The establishment of a zebrafish model of fetal alcohol syndrome will greatly enhance the ability to perform genetic studies.

The second set of ongoing research projects in my lab examine the role of Sonic hedgehog in cranio-facial development and how deficiencies in shh result in holoprosencephaly. These studies are also examining other genes which have been linked to holoprosencephaly, primarily the transcription factor zic, a gene related to the gli transcription factors, which are downstream of shh.

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