Monday, March 26, 2012 - Minot State Universityyourspace.minotstateu.edu/paul.lepp/Concepts... ·...

Monday, March 26, 2012

The First Stem Cell Patient

• T.J. Atchinson• 21years-old• Nursing student at U.

of South Alabama

• Car accident Sept. 25, 2010


• Severed spinal column at T7 vertebra

• Candidate for phase 1 stem cell clinical trial because of age, health and type of injury


What is a stem cell?


How are embryonic stem cells different from other types of stem cells?


Ethical dilemmas

• The Atchinsons are devote Southern Baptists and strong opponents of abortion.


Why is there controversy surrounding the use of embryonic stem cells?


Ethical dilemmas

• Some patient’s rights advocates believe that recently injured patients can not make a rational decision.

“They said this could be the best thing for you to get better,” Atchison said. “To anyone who’s paralyzed, that’s what you want to hear.”


Was TJ making a rational decision?


Ethical dilemmas

• One of the possible side effects of treatment is cancer. Why? What is cancer?


Gastrulation


Figure 29.19


Embryogenesis

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22• Lemons & McGinnis, Science, 2006


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Bithorax mutant (ubx)

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• Lemons & McGinnis, Science, 2006


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Polydactylism

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Current Biology 16, 371–377, February 21, 2006 ª2006 Elsevier Ltd All rights reserved DOI 10.1016/j.cub.2005.12.047

ReportThe Development of ArchosaurianFirst-Generation Teethin a Chicken Mutant

Matthew P. Harris,1,3,* Sean M. Hasso,1

Mark W.J. Ferguson,2 and John F. Fallon1,*1Department of AnatomyUniversity of Wisconsin1300 University AvenueMadison, Wisconsin 537062Faculty of Life SciencesUniversity of ManchesterManchester M13 9PTUnited Kingdom

Summary

Modern birds do not have teeth. Rather, they developa specialized keratinized structure, called the rham-photheca, that covers the mandible, maxillae, and pre-maxillae. Although recombination studies have shownthat the avian epidermis can respond to tooth-induc-tive cues from mouse or lizard oral mesenchyme andparticipate in tooth formation [1, 2], attempts to initiatetooth development de novo in birds have failed. Here,we describe the formation of teeth in the talpid2

chicken mutant, including the developmental pro-cesses and early molecular changes associated withthe formation of teeth. Additionally, we show recapitu-lation of the early events seen in talpid2 after in vivoactivation of b-catenin in wild-type embryos. We com-pare the formation of teeth in the talpid2 mutant withthat in the alligator and show the formation of decid-edly archosaurian (crocodilian) first-generation teethin an avian embryo. The formation of teeth in the mu-tant is coupled with alterations in the specification ofthe oral/aboral boundary of the jaw. We propose anepigenetic model of the developmental modificationof dentition in avian evolution; in this model, changesin the relative position of a lateral signaling center overcompetent odontogenic mesenchyme led to loss ofteeth in avians while maintaining tooth developmentalpotential.

Results and Discussion

Early dinosaurian ancestors of birds (avialan and nona-vialan theropods [3]) possessed conical teeth homolo-gous to those of their reptilian ancestors; however, avianteeth were lost at least 70–80 million years ago. In addi-tion, teeth have been independently lost several timeswithin nonavialan theropods, avialans, and chelonians;this loss is correlated with the formation of the horny,keratinized epithelium and the beak [4–6]. In the epider-mis of embryonic birds, there remains a transient

thickening that is comparable to the early formation ofthe dental lamina in the mouse [7, 8]; this structure re-gresses, and invaginations associated with tooth forma-tion do not form. However, the avian oral epithelium hasthe developmental capacity to initiate tooth develop-mental programs with underlying grafts of non-avianoral ectomesenchyme [1, 2] as well as avian mesen-chyme competent to form integumentary appendages[8]. Additionally, the avian mandibular mesenchymecan respond to inductive signals frommousemandibularepithelium and form tooth-like structures with differenti-ation of pre-dentine [9]. This demonstration of dormantdevelopmental programs revealed in recombination ex-periments emphasized the study of experimental ata-visms, such as ‘‘Hen’s Teeth,’’ in understanding therole of development in evolutionary change [1, 10–12].Given the latent capacity of the chicken mandibular epi-dermis to participate in tooth morphogenesis, the prob-lem remains as to what extent tooth programs are main-tained in birds in an in vivo context of the developing jawandhow this relates to the lossof avian teeth inevolution.Here, we describe the first evidence of tooth develop-

mental programs and morphology initiated in an extantbird as a result of either mutation or experimentationand, importantly, without xenoplastic tissue grafts or tis-sue manipulation. Because birds and mammals evolvedin parallel (avian andmammalian lineages shared a com-mon ancestor in the early amniotes at least 300 millionyears ago), the relevant comparison for avian tooth de-velopmental programs is within the archosaurs, withcrocodilians, the closest living relative of birds. Amongother things, crocodilian tooth development, e.g., in alli-gators, differs from that of mammals in that the forma-tion of first-generation teeth is initiated as an evagina-tion of the integument rather than an invagination ofthe epithelium [13]. The subsequent generations of toothformation in the alligator form epithelial invaginations asin mammals. This pattern of tooth formation is thoughtto be similar for other reptiles [13]. Our analysis ofthe developmental programs of tooth formation of thetalpid2 (ta2) chicken shows similarity with the formationof first-generation crocodilian teeth. In addition, we pro-pose that the oral/aboral boundary establishes a signal-ing center that, depending on its apposition to under-lying competent mesenchyme, controls the initiationand suppression of teeth.

Developmental Specification of Teeth in ta2

ta2 is an autosomal recessive mutation that affects thedevelopment of several organ systems in the chick[14]. We observed the formation of integumentary out-growths on the developing jaw of 14- to 16-day-old ta2

embryos (E14–E16). These structures were only formedin close association with the lateral boundary of the oralcavity and were found at the distal boundary of the jaw(Figures 1B and 1D). On the mandible, these structureswere equally spaced in a line positioned more centrallyin the oral cavity than the formation of the distal lamellae

*Correspondence: [email protected] (M.P.H.);[email protected] (J.F.F.)3Present address: Max Planck Institute fur Entwicklungsbiologie,Abt. Genetik Spemanstrasse 35, 72076 Tubingen, Germany.

of the wild-type chick jaw (compare Figures 1A and 1B).The maxilla, deformed in the mutant, showed similaroutgrowths clumped at the altered distal margin of thejaw (Figure 1D).ta2 embryos rarely survive past E12. However, we

were able to isolate several near-hatching stages(n = 5). The loss of the rhamphotheca during preparationfor skeletal analysis in several of these specimens un-covered the formation of a set of conical, saber-shapedoutgrowths from the distal mandible; these outgrowths

had previously been hidden by the horny epidermis ofthe beak (Figures 1E and 1F; 100%, n = 3). Underlyingthese outgrowths, remodelling of the mandible can beseen (Figures 1E and 1F). Furthermore, sectioning ofnear-hatching-staged ta2 jaws with an intact rhampho-theca revealed the formation of a lamina at the lateraloral/aboral boundary (Figures 1G and 1H). At the baseof the lamina, there was evidence of differentiation ofthe surface epithelial cells away from the normal kerati-nized squamous morphology (Figure 1H).

Figure 1. Oral Appendages in the ta2 Mutant and Anatomical Similarity with First-Generation Embryonic Teeth of the Alligator

(A–D) Formation of meristic integumentary appendages on the distal mandible and premaxillae of E16 ta2 chick (B and D) and wild-type siblings(A and C). Magnified views of the formations at the distal tip of the jaw shown in insets; meristic, conical outgrowths of the mutant indicated witharrowheads.(E and F) Mandible of near-hatching ta2 jaw stainedwith alizarin red. The rhamphotheca was removed in preparation, uncovering underlying con-ical, saber-shaped outgrowths at the distal tip (arrow indicates remodeling of bone matrix underlying the tooth formations).(G and H) Giesma-stained histological section of a near-hatching specimen with rhamphotheca attached, showing the formation of a laminaalong the lateral margin of the mandible. (H) Magnification of differentiated cells in the crest of the laminar fold shown in (G).(I–N) Haematoxyalin- and eosin-stained histological sections of forming oral appendages of E14 ta2 embryos. In (I)–(J), the lower jaw of wild-type(wt) sibling and ta2 embryos (ta2) shows formation of outgrowths in more medial positions of the oral cavity. The oral/aboral boundary, indicatedby a shift of epithelial differentiation, is marked with a dotted line (G, I, J, K, and N). In (K), (M), and (N), tooth primordia from ta2 show specificdifferentiation of the dental mesenchyme, including central vascularization and circumferential, immature odontoblasts (white arrowheads).(L) shows a close-up of the distal portion of (K).(O–P) Haematoxyalin- and eosin-stained histological sections of rudimentary teeth of stage-17 alligator [40] embryo. Putative dentine matrix isseen at the distal tip of the ta2 dental structures and in the alligator (yellow arrowheads, [K–P]). The scale bar equals 50 mm in all panels except (L)and (H), in which the scale bar equals 20 mm.

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